{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:06:33Z","timestamp":1793736393944,"version":"4.6.1"},"reference-count":215,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Gastroenterol Hepatol"],"DOI":"10.1038\/s41575-026-01242-4","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:21:38Z","timestamp":1788452498000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Building and regenerating intestines by manipulating intestinal stem cells"],"prefix":"10.1038","author":[{"given":"Calvin J.","family":"Kuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Blutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Donowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4813-4249","authenticated-orcid":false,"given":"Mary K.","family":"Estes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan","family":"Guha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6254-7082","authenticated-orcid":false,"given":"Ophir D.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9963-430X","authenticated-orcid":false,"given":"Linheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-517X","authenticated-orcid":false,"given":"Joyce C.","family":"Niland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f3nio J. M.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2828-1727","authenticated-orcid":false,"given":"Ramesh A.","family":"Shivdasani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Spence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol J.","family":"Swanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5730-3019","authenticated-orcid":false,"given":"Timothy C.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9826-7261","authenticated-orcid":false,"given":"Kelley S.","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Zachos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3112-7541","authenticated-orcid":false,"given":"Michael A.","family":"Helmrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"1242_CR1","unstructured":"Hasler, W. L. & Owyang, C. in Harrison\u2019s Principles of Internal Medicine 22nd edn (eds Longo, D. L. et al.) Ch. 332 (McGraw Hill, 2025)."},{"key":"1242_CR2","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.stem.2023.03.008","volume":"30","author":"I Banjac","year":"2023","unstructured":"Banjac, I., Maimets, M. & Jensen, K. B. Maintenance of high-turnover tissues during and beyond homeostasis. Cell Stem Cell 30, 348\u2013361 (2023).","journal-title":"Cell Stem Cell"},{"key":"1242_CR3","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/s41580-020-0278-0","volume":"22","author":"J Beumer","year":"2021","unstructured":"Beumer, J. & Clevers, H. Cell fate specification and differentiation in the adult mammalian intestine. Nat. Rev. Mol. Cell Biol. 22, 39\u201353 (2021).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1242_CR4","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/j.tcb.2018.08.001","volume":"28","author":"AJM Santos","year":"2018","unstructured":"Santos, A. J. M., Lo, Y. H., Mah, A. T. & Kuo, C. J. The intestinal stem cell niche: homeostasis and adaptations. Trends Cell Biol. 28, 1062\u20131078 (2018).","journal-title":"Trends Cell Biol."},{"key":"1242_CR5","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1016\/j.jcmgh.2022.02.007","volume":"13","author":"J Burclaff","year":"2022","unstructured":"Burclaff, J. et al. A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics. Cell. Mol. Gastroenterol. Hepatol. 13, 1554\u20131589 (2022).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR6","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.cell.2019.06.029","volume":"178","author":"CS Smillie","year":"2019","unstructured":"Smillie, C. S. et al. Intra- and inter-cellular rewiring of the human colon during ulcerative colitis. Cell 178, 714\u2013730.e722 (2019).","journal-title":"Cell"},{"key":"1242_CR7","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41586-019-0992-y","volume":"567","author":"K Parikh","year":"2019","unstructured":"Parikh, K. et al. Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature 567, 49\u201355 (2019).","journal-title":"Nature"},{"key":"1242_CR8","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1053\/j.gastro.2025.01.248","volume":"169","author":"Y Wakisaka","year":"2025","unstructured":"Wakisaka, Y. et al. Understanding the differentiation pathway to bestrophin 4-positive cells in human colonic epithelium. Gastroenterology 169, 154\u2013157.e155 (2025).","journal-title":"Gastroenterology"},{"key":"1242_CR9","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1002\/aja.1001410407","volume":"141","author":"H Cheng","year":"1974","unstructured":"Cheng, H. & Leblond, C. P. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian theory of the origin of the four epithelial cell types. Am. J. Anat. 141, 537\u2013561 (1974).","journal-title":"Am. J. Anat."},{"key":"1242_CR10","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/bies.10028","volume":"24","author":"E Marshman","year":"2002","unstructured":"Marshman, E., Booth, C. & Potten, C. S. The intestinal epithelial stem cell. Bioessays 24, 91\u201398 (2002).","journal-title":"Bioessays"},{"key":"1242_CR11","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.cell.2013.07.004","volume":"154","author":"H Clevers","year":"2013","unstructured":"Clevers, H. The intestinal crypt, a prototype stem cell compartment. Cell 154, 274\u2013284 (2013).","journal-title":"Cell"},{"key":"1242_CR12","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.1242\/jcs.115.11.2381","volume":"115","author":"CS Potten","year":"2002","unstructured":"Potten, C. S., Owen, G. & Booth, D. Intestinal stem cells protect their genome by selective segregation of template DNA strands. J. Cell Sci. 115, 2381\u20132388 (2002).","journal-title":"J. Cell Sci."},{"key":"1242_CR13","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/aja.1001240303","volume":"124","author":"J Merzel","year":"1969","unstructured":"Merzel, J. & Leblond, C. P. Origin and renewal of goblet cells in the epithelium of the mouse small intestine. Am. J. Anat. 124, 281\u2013305 (1969).","journal-title":"Am. J. Anat."},{"key":"1242_CR14","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/nature06196","volume":"449","author":"N Barker","year":"2007","unstructured":"Barker, N. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003\u20131007 (2007).","journal-title":"Nature"},{"key":"1242_CR15","doi-asserted-by":"publisher","first-page":"3079","DOI":"10.1038\/emboj.2012.166","volume":"31","author":"J Munoz","year":"2012","unstructured":"Munoz, J. et al. The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent \u2018+4\u2019 cell markers. EMBO J. 31, 3079\u20133091 (2012).","journal-title":"EMBO J."},{"key":"1242_CR16","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1073\/pnas.1118857109","volume":"109","author":"KS Yan","year":"2012","unstructured":"Yan, K. S. et al. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc. Natl Acad. Sci. USA 109, 466\u2013471 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR17","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nature10408","volume":"478","author":"H Tian","year":"2011","unstructured":"Tian, H. et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478, 255\u2013259 (2011).","journal-title":"Nature"},{"key":"1242_CR18","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.1016\/j.cell.2024.05.004","volume":"187","author":"E Malagola","year":"2024","unstructured":"Malagola, E. et al. Isthmus progenitor cells contribute to homeostatic cellular turnover and support regeneration following intestinal injury. Cell 187, 3056\u20133071.e3017 (2024).","journal-title":"Cell"},{"key":"1242_CR19","doi-asserted-by":"publisher","first-page":"3039","DOI":"10.1016\/j.cell.2024.05.001","volume":"187","author":"C Capdevila","year":"2024","unstructured":"Capdevila, C. et al. Time-resolved fate mapping identifies the intestinal upper crypt zone as an origin of Lgr5+ crypt base columnar cells. Cell 187, 3039\u20133055.e3014 (2024).","journal-title":"Cell"},{"key":"1242_CR20","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1126\/science.1180794","volume":"327","author":"L Li","year":"2010","unstructured":"Li, L. & Clevers, H. Coexistence of quiescent and active adult stem cells in mammals. Science 327, 542\u2013545 (2010).","journal-title":"Science"},{"key":"1242_CR21","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1053\/j.gastro.2008.01.079","volume":"134","author":"DH Scoville","year":"2008","unstructured":"Scoville, D. H., Sato, T., He, X. C. & Li, L. Current view: intestinal stem cells and signaling. Gastroenterology 134, 849\u2013864 (2008).","journal-title":"Gastroenterology"},{"key":"1242_CR22","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/ng.165","volume":"40","author":"E Sangiorgi","year":"2008","unstructured":"Sangiorgi, E. & Capecchi, M. R. Bmi1 is expressed in vivo in intestinal stem cells. Nat. Genet. 40, 915\u2013920 (2008).","journal-title":"Nat. Genet."},{"key":"1242_CR23","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.stem.2015.04.013","volume":"16","author":"S Asfaha","year":"2015","unstructured":"Asfaha, S. et al. Krt19+\/Lgr5\u2212 cells are radioresistant cancer-initiating stem cells in the colon and intestine. Cell Stem Cell 16, 627\u2013638 (2015).","journal-title":"Cell Stem Cell"},{"key":"1242_CR24","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/s41586-019-1154-y","volume":"569","author":"A Ayyaz","year":"2019","unstructured":"Ayyaz, A. et al. Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell. Nature 569, 121\u2013125 (2019).","journal-title":"Nature"},{"key":"1242_CR25","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.stem.2017.02.007","volume":"20","author":"FM Barriga","year":"2017","unstructured":"Barriga, F. M. et al. Mex3a marks a slowly dividing subpopulation of Lgr5+ intestinal stem cells. Cell Stem Cell 20, 801\u2013816.e807 (2017).","journal-title":"Cell Stem Cell"},{"key":"1242_CR26","doi-asserted-by":"publisher","first-page":"G796","DOI":"10.1152\/ajpgi.00126.2019","volume":"318","author":"S Karmakar","year":"2020","unstructured":"Karmakar, S., Deng, L., He, X. C. & Li, L. Intestinal epithelial regeneration: active versus reserve stem cells and plasticity mechanisms. Am. J. Physiol. Gastrointest. Liver Physiol. 318, G796\u2013G802 (2020).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"1242_CR27","doi-asserted-by":"publisher","first-page":"2403","DOI":"10.1016\/j.celrep.2015.11.035","volume":"13","author":"CA Richmond","year":"2015","unstructured":"Richmond, C. A. et al. Dormant intestinal stem cells are regulated by PTEN and nutritional status. Cell Rep. 13, 2403\u20132411 (2015).","journal-title":"Cell Rep."},{"key":"1242_CR28","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1126\/science.1213214","volume":"334","author":"N Takeda","year":"2011","unstructured":"Takeda, N. et al. Interconversion between intestinal stem cell populations in distinct niches. Science 334, 1420\u20131424 (2011).","journal-title":"Science"},{"key":"1242_CR29","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.devcel.2024.10.021","volume":"60","author":"L Deng","year":"2025","unstructured":"Deng, L. et al. Frizzled5 controls murine intestinal epithelial cell plasticity through organization of chromatin accessibility. Dev. Cell 60, 352\u2013363.e356 (2025).","journal-title":"Dev. Cell"},{"key":"1242_CR30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.stem.2019.12.011","volume":"26","author":"K Murata","year":"2020","unstructured":"Murata, K. et al. Ascl2-dependent cell dedifferentiation drives regeneration of ablated intestinal stem cells. Cell Stem Cell 26, 377\u2013390.e376 (2020).","journal-title":"Cell Stem Cell"},{"key":"1242_CR31","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1053\/j.gastro.2016.04.049","volume":"151","author":"N Li","year":"2016","unstructured":"Li, N., Nakauka-Ddamba, A., Tobias, J., Jensen, S. T. & Lengner, C. J. Mouse label-retaining cells are molecularly and functionally distinct from reserve intestinal stem cells. Gastroenterology 151, 298\u2013310.e297 (2016).","journal-title":"Gastroenterology"},{"key":"1242_CR32","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature11965","volume":"495","author":"SJ Buczacki","year":"2013","unstructured":"Buczacki, S. J. et al. Intestinal label-retaining cells are secretory precursors expressing Lgr5. Nature 495, 65\u201369 (2013).","journal-title":"Nature"},{"key":"1242_CR33","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1038\/ncb2581","volume":"14","author":"JH van Es","year":"2012","unstructured":"van Es, J. H. et al. Dll1+ secretory progenitor cells revert to stem cells upon crypt damage. Nat. Cell Biol. 14, 1099\u20131104 (2012).","journal-title":"Nat. Cell Biol."},{"key":"1242_CR34","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.stem.2016.01.001","volume":"18","author":"PW Tetteh","year":"2016","unstructured":"Tetteh, P. W. et al. Replacement of lost Lgr5-positive stem cells through plasticity of their enterocyte-lineage daughters. Cell Stem Cell 18, 203\u2013213 (2016).","journal-title":"Cell Stem Cell"},{"key":"1242_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038965","volume":"7","author":"S Roth","year":"2012","unstructured":"Roth, S. et al. Paneth cells in intestinal homeostasis and tissue injury. PLoS ONE 7, e38965 (2012).","journal-title":"PLoS ONE"},{"key":"1242_CR36","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1053\/j.gastro.2015.07.004","volume":"149","author":"KC Roche","year":"2015","unstructured":"Roche, K. C. et al. SOX9 maintains reserve stem cells and preserves radioresistance in mouse small intestine. Gastroenterology 149, 1553\u20131563.e1510 (2015).","journal-title":"Gastroenterology"},{"key":"1242_CR37","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.stem.2018.05.002","volume":"23","author":"S Yu","year":"2018","unstructured":"Yu, S. et al. Paneth cell multipotency induced by notch activation following injury. Cell Stem Cell 23, 46\u201359.e45 (2018).","journal-title":"Cell Stem Cell"},{"key":"1242_CR38","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/s41586-018-0257-1","volume":"559","author":"YM Nusse","year":"2018","unstructured":"Nusse, Y. M. et al. Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche. Nature 559, 109\u2013113 (2018).","journal-title":"Nature"},{"key":"1242_CR39","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.stem.2017.05.001","volume":"21","author":"U Jadhav","year":"2017","unstructured":"Jadhav, U. et al. Dynamic reorganization of chromatin accessibility signatures during dedifferentiation of secretory precursors into Lgr5+ intestinal stem cells. Cell Stem Cell 21, 65\u201377.e65 (2017).","journal-title":"Cell Stem Cell"},{"key":"1242_CR40","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/s41586-024-07952-6","volume":"634","author":"L Huang","year":"2024","unstructured":"Huang, L. et al. Tuft cells act as regenerative stem cells in the human intestine. Nature 634, 929\u2013935 (2024).","journal-title":"Nature"},{"key":"1242_CR41","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1016\/j.devcel.2025.03.014","volume":"60","author":"NR Smith","year":"2025","unstructured":"Smith, N. R. et al. Dual states of murine Bmi1-expressing intestinal stem cells drive epithelial development utilizing non-canonical Wnt signaling. Dev. Cell 60, 2177\u20132191.e5 https:\/\/doi.org\/10.1016\/j.devcel.2025.03.014 (2025).","journal-title":"Dev. Cell"},{"key":"1242_CR42","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/nature12903","volume":"506","author":"TH Kim","year":"2014","unstructured":"Kim, T. H. et al. Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity. Nature 506, 511\u2013515 (2014).","journal-title":"Nature"},{"key":"1242_CR43","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1053\/j.gastro.2011.07.050","volume":"141","author":"T Sato","year":"2011","unstructured":"Sato, T. et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett\u2019s epithelium. Gastroenterology 141, 1762\u20131772 (2011).","journal-title":"Gastroenterology"},{"key":"1242_CR44","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/nature07935","volume":"459","author":"T Sato","year":"2009","unstructured":"Sato, T. et al. Single Lgr5 stem cells build crypt\u2013villus structures in vitro without a mesenchymal niche. Nature 459, 262\u2013265 (2009).","journal-title":"Nature"},{"key":"1242_CR45","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nm.1951","volume":"15","author":"A Ootani","year":"2009","unstructured":"Ootani, A. et al. Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat. Med. 15, 701\u2013706 (2009).","journal-title":"Nat. Med."},{"key":"1242_CR46","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nature09691","volume":"470","author":"JR Spence","year":"2011","unstructured":"Spence, J. R. et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470, 105\u2013109 (2011).","journal-title":"Nature"},{"key":"1242_CR47","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1038\/nm.3737","volume":"20","author":"CL Watson","year":"2014","unstructured":"Watson, C. L. et al. An in vivo model of human small intestine using pluripotent stem cells. Nat. Med. 20, 1310\u20131314 (2014).","journal-title":"Nat. Med."},{"key":"1242_CR48","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/s41586-021-03247-2","volume":"592","author":"S Sugimoto","year":"2021","unstructured":"Sugimoto, S. et al. An organoid-based organ-repurposing approach to treat short bowel syndrome. Nature 592, 99\u2013104 (2021).","journal-title":"Nature"},{"key":"1242_CR49","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1038\/s41587-022-01558-x","volume":"41","author":"C Bouffi","year":"2023","unstructured":"Bouffi, C. et al. In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice. Nat. Biotechnol. 41, 824\u2013831 (2023).","journal-title":"Nat. Biotechnol."},{"key":"1242_CR50","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s41586-024-07716-2","volume":"632","author":"AJM Santos","year":"2024","unstructured":"Santos, A. J. M. et al. A human autoimmune organoid model reveals IL-7 function in coeliac disease. Nature 632, 401\u2013410 (2024).","journal-title":"Nature"},{"key":"1242_CR51","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41586-024-07791-5","volume":"633","author":"T Recaldin","year":"2024","unstructured":"Recaldin, T. et al. Human organoids with an autologous tissue-resident immune compartment. Nature 633, 165\u2013173 (2024).","journal-title":"Nature"},{"key":"1242_CR52","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.stem.2024.05.007","volume":"31","author":"O Mitrofanova","year":"2024","unstructured":"Mitrofanova, O. et al. Bioengineered human colon organoids with in vivo-like cellular complexity and function. Cell Stem Cell 31, 1175\u20131186.e1177 (2024).","journal-title":"Cell Stem Cell"},{"key":"1242_CR53","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1038\/s41586-020-2724-8","volume":"585","author":"M Nikolaev","year":"2020","unstructured":"Nikolaev, M. et al. Homeostatic mini-intestines through scaffold-guided organoid morphogenesis. Nature 585, 574\u2013578 (2020).","journal-title":"Nature"},{"key":"1242_CR54","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1101\/gad.267103","volume":"17","author":"D Pinto","year":"2003","unstructured":"Pinto, D., Gregorieff, A., Begthel, H. & Clevers, H. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes. Dev. 17, 1709\u20131713 (2003).","journal-title":"Genes. Dev."},{"key":"1242_CR55","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1073\/pnas.2536800100","volume":"101","author":"F Kuhnert","year":"2004","unstructured":"Kuhnert, F. et al. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc. Natl Acad. Sci. USA 101, 266\u2013271 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR56","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1038\/ng1430","volume":"36","author":"XC He","year":"2004","unstructured":"He, X. C. et al. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt\u2013\u03b2-catenin signaling. Nat. Genet. 36, 1117\u20131121 (2004).","journal-title":"Nat. Genet."},{"key":"1242_CR57","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1126\/science.1093587","volume":"303","author":"AP Haramis","year":"2004","unstructured":"Haramis, A. P. et al. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 303, 1684\u20131686 (2004).","journal-title":"Science"},{"key":"1242_CR58","doi-asserted-by":"publisher","first-page":"E3173","DOI":"10.1073\/pnas.1713510115","volume":"115","author":"G Greicius","year":"2018","unstructured":"Greicius, G. et al. PDGFR\u03b1+ pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo. Proc. Natl Acad. Sci. USA 115, E3173\u2013E3181 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR59","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1242\/dev.104976","volume":"141","author":"Z Kabiri","year":"2014","unstructured":"Kabiri, Z. et al. Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts. Development 141, 2206\u20132215 (2014).","journal-title":"Development"},{"key":"1242_CR60","doi-asserted-by":"publisher","first-page":"3698","DOI":"10.1016\/j.celrep.2019.02.101","volume":"26","author":"ON Karpus","year":"2019","unstructured":"Karpus, O. N. et al. Colonic CD90+ crypt fibroblasts secrete semaphorins to support epithelial growth. Cell Rep. 26, 3698\u20133708.e3695 (2019).","journal-title":"Cell Rep."},{"key":"1242_CR61","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.stem.2020.01.008","volume":"26","author":"N McCarthy","year":"2020","unstructured":"McCarthy, N. et al. Distinct mesenchymal cell populations generate the essential intestinal BMP signaling gradient. Cell Stem Cell 26, 391\u2013402.e395 (2020).","journal-title":"Cell Stem Cell"},{"key":"1242_CR62","doi-asserted-by":"publisher","first-page":"E506","DOI":"10.1073\/pnas.1620059114","volume":"114","author":"I Stzepourginski","year":"2017","unstructured":"Stzepourginski, I. et al. CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury. Proc. Natl Acad. Sci. USA 114, E506\u2013E513 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR63","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/j.celrep.2016.03.088","volume":"15","author":"T Valenta","year":"2016","unstructured":"Valenta, T. et al. Wnt ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis. Cell Rep. 15, 911\u2013918 (2016).","journal-title":"Cell Rep."},{"key":"1242_CR64","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.stem.2023.03.004","volume":"30","author":"J Kraiczy","year":"2023","unstructured":"Kraiczy, J. et al. Graded BMP signaling within intestinal crypt architecture directs self-organization of the Wnt-secreting stem cell niche. Cell Stem Cell 30, 433\u2013449.e438 (2023).","journal-title":"Cell Stem Cell"},{"key":"1242_CR65","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nature16466","volume":"529","author":"EE Storm","year":"2016","unstructured":"Storm, E. E. et al. Targeting PTPRK\u2013RSPO3 colon tumours promotes differentiation and loss of stem-cell function. Nature 529, 97\u2013100 (2016).","journal-title":"Nature"},{"key":"1242_CR66","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nature22313","volume":"545","author":"KS Yan","year":"2017","unstructured":"Yan, K. S. et al. Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal. Nature 545, 238\u2013242 (2017).","journal-title":"Nature"},{"key":"1242_CR67","doi-asserted-by":"publisher","first-page":"e165566","DOI":"10.1172\/jci.insight.165566","volume":"8","author":"CJ Childs","year":"2023","unstructured":"Childs, C. J. et al. EPIREGULIN creates a developmental niche for spatially organized human intestinal enteroids. JCI Insight 8, e165566 https:\/\/doi.org\/10.1172\/jci.insight.165566 (2023).","journal-title":"JCI Insight"},{"key":"1242_CR68","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.stem.2020.06.021","volume":"27","author":"T Jarde","year":"2020","unstructured":"Jarde, T. et al. Mesenchymal niche-derived neuregulin-1 drives intestinal stem cell proliferation and regeneration of damaged epithelium. Cell Stem Cell 27, 646\u2013662.e647 (2020).","journal-title":"Cell Stem Cell"},{"key":"1242_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03638-6","volume":"9","author":"A Sehgal","year":"2018","unstructured":"Sehgal, A. et al. The role of CSF1R-dependent macrophages in control of the intestinal stem-cell niche. Nat. Commun. 9, 1272 (2018).","journal-title":"Nat. Commun."},{"key":"1242_CR70","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/nri3608","volume":"14","author":"LW Peterson","year":"2014","unstructured":"Peterson, L. W. & Artis, D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 14, 141\u2013153 (2014).","journal-title":"Nat. Rev. Immunol."},{"key":"1242_CR71","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1016\/j.cell.2018.10.008","volume":"175","author":"M Biton","year":"2018","unstructured":"Biton, M. et al. T helper cell cytokines modulate intestinal stem cell renewal and differentiation. Cell 175, 1307\u20131320.e1322 (2018).","journal-title":"Cell"},{"key":"1242_CR72","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13096","volume":"7","author":"S Saha","year":"2016","unstructured":"Saha, S. et al. Macrophage-derived extracellular vesicle-packaged WNTs rescue intestinal stem cells and enhance survival after radiation injury. Nat. Commun. 7, 13096 (2016).","journal-title":"Nat. Commun."},{"key":"1242_CR73","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/j.stem.2022.05.007","volume":"29","author":"RE Niec","year":"2022","unstructured":"Niec, R. E. et al. Lymphatics act as a signaling hub to regulate intestinal stem cell activity. Cell Stem Cell 29, 1067\u20131082.e1018 (2022).","journal-title":"Cell Stem Cell"},{"key":"1242_CR74","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1016\/j.stem.2022.06.013","volume":"29","author":"N Goto","year":"2022","unstructured":"Goto, N. et al. Lymphatics and fibroblasts support intestinal stem cells in homeostasis and injury. Cell Stem Cell 29, 1246\u20131261.e1246 (2022).","journal-title":"Cell Stem Cell"},{"key":"1242_CR75","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.stem.2022.07.007","volume":"29","author":"B Palikuqi","year":"2022","unstructured":"Palikuqi, B. et al. Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury. Cell Stem Cell 29, 1262\u20131272.e1265 (2022).","journal-title":"Cell Stem Cell"},{"key":"1242_CR76","doi-asserted-by":"publisher","first-page":"G2","DOI":"10.1152\/ajpgi.00075.2005","volume":"289","author":"DW Powell","year":"2005","unstructured":"Powell, D. W., Adegboyega, P. A., Di Mari, J. F. & Mifflin, R. C. Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer. Am. J. Physiol. Gastrointest. Liver Physiol. 289, G2\u2013G7 (2005).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"1242_CR77","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1146\/annurev.physiol.70.113006.100646","volume":"73","author":"DW Powell","year":"2011","unstructured":"Powell, D. W., Pinchuk, I. V., Saada, J. I., Chen, X. & Mifflin, R. C. Mesenchymal cells of the intestinal lamina propria. Annu. Rev. Physiol. 73, 213\u2013237 (2011).","journal-title":"Annu. Rev. Physiol."},{"key":"1242_CR78","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/s41586-018-0084-4","volume":"557","author":"M Shoshkes-Carmel","year":"2018","unstructured":"Shoshkes-Carmel, M. et al. Subepithelial telocytes are an important source of Wnts that supports intestinal crypts. Nature 557, 242\u2013246 https:\/\/doi.org\/10.1038\/s41586-018-0084-4 (2018).","journal-title":"Nature"},{"key":"1242_CR79","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.devcel.2023.02.012","volume":"58","author":"N McCarthy","year":"2023","unstructured":"McCarthy, N. et al. Smooth muscle contributes to the development and function of a layered intestinal stem cell niche. Dev. Cell 58, 550\u2013564.e556 (2023).","journal-title":"Dev. Cell"},{"key":"1242_CR80","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/s41556-020-0567-z","volume":"22","author":"N McCarthy","year":"2020","unstructured":"McCarthy, N., Kraiczy, J. & Shivdasani, R. A. Cellular and molecular architecture of the intestinal stem cell niche. Nat. Cell Biol. 22, 1033\u20131041 (2020).","journal-title":"Nat. Cell Biol."},{"key":"1242_CR81","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/s41422-022-00643-9","volume":"32","author":"M Deng","year":"2022","unstructured":"Deng, M. et al. Lepr+ mesenchymal cells sense diet to modulate intestinal stem\/progenitor cells via Leptin\u2013Igf1 axis. Cell Res. 32, 670\u2013686 (2022).","journal-title":"Cell Res."},{"key":"1242_CR82","doi-asserted-by":"publisher","first-page":"e163380","DOI":"10.1172\/JCI163380","volume":"132","author":"K Kurokawa","year":"2022","unstructured":"Kurokawa, K., Wang, T. C. & Hayakawa, Y. R-spondin 3 governs secretory differentiation in the gastric oxyntic glands. J. Clin. Invest. 132, e163380 https:\/\/doi.org\/10.1172\/JCI163380 (2022).","journal-title":"J. Clin. Invest."},{"key":"1242_CR83","doi-asserted-by":"publisher","first-page":"e151363","DOI":"10.1172\/JCI151363","volume":"132","author":"AS Fischer","year":"2022","unstructured":"Fischer, A. S. et al. R-spondin\/YAP axis promotes gastric oxyntic gland regeneration and Helicobacter pylori-associated metaplasia in mice. J. Clin. Invest. 132, e151363 https:\/\/doi.org\/10.1172\/JCI151363 (2022).","journal-title":"J. Clin. Invest."},{"key":"1242_CR84","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.stem.2021.10.004","volume":"29","author":"MB Baghdadi","year":"2022","unstructured":"Baghdadi, M. B. et al. Enteric glial cell heterogeneity regulates intestinal stem cell niches. Cell Stem Cell 29, 86\u2013100.e106 (2022).","journal-title":"Cell Stem Cell"},{"key":"1242_CR85","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216427","volume":"15","author":"C Wallaeys","year":"2023","unstructured":"Wallaeys, C., Garcia-Gonzalez, N. & Libert, C. Paneth cells as the cornerstones of intestinal and organismal health: a primer. EMBO Mol. Med. 15, e16427 (2023).","journal-title":"EMBO Mol. Med."},{"key":"1242_CR86","doi-asserted-by":"publisher","first-page":"3932","DOI":"10.1073\/pnas.1113890109","volume":"109","author":"TH Kim","year":"2012","unstructured":"Kim, T. H., Escudero, S. & Shivdasani, R. A. Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells. Proc. Natl Acad. Sci. USA 109, 3932\u20133937 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR87","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/s41575-022-00675-x","volume":"19","author":"JK Gustafsson","year":"2022","unstructured":"Gustafsson, J. K. & Johansson, M. E. V. The role of goblet cells and mucus in intestinal homeostasis. Nat. Rev. Gastroenterol. Hepatol. 19, 785\u2013803 (2022).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"1242_CR88","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.trecan.2016.06.006","volume":"2","author":"S Lamprecht","year":"2016","unstructured":"Lamprecht, S. & Fich, A. Small intestinal cancer: why the rarity? Trends Cancer 2, 395\u2013397 (2016).","journal-title":"Trends Cancer"},{"key":"1242_CR89","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1038\/s41586-025-08591-1","volume":"640","author":"X Zhi","year":"2025","unstructured":"Zhi, X. et al. Nociceptive neurons promote gastric tumour progression via a CGRP\u2013RAMP1 axis. Nature 640, 802\u2013810 (2025).","journal-title":"Nature"},{"key":"1242_CR90","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24768-3","volume":"8","author":"M Puzan","year":"2018","unstructured":"Puzan, M., Hosic, S., Ghio, C. & Koppes, A. Enteric nervous system regulation of intestinal stem cell differentiation and epithelial monolayer function. Sci. Rep. 8, 6313 (2018).","journal-title":"Sci. Rep."},{"key":"1242_CR91","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.jcmgh.2023.10.007","volume":"17","author":"Z Jiang","year":"2024","unstructured":"Jiang, Z. et al. Microbial-dependent recruitment of immature myeloid cells promotes intestinal regeneration. Cell. Mol. Gastroenterol. Hepatol. 17, 321\u2013346 (2024).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR92","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.stem.2017.11.001","volume":"22","author":"S Yui","year":"2018","unstructured":"Yui, S. et al. YAP\/TAZ-dependent reprogramming of colonic epithelium links ECM remodeling to tissue regeneration. Cell Stem Cell 22, 35\u201349.e37 (2018).","journal-title":"Cell Stem Cell"},{"key":"1242_CR93","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41586-019-1146-y","volume":"569","author":"D Serra","year":"2019","unstructured":"Serra, D. et al. Self-organization and symmetry breaking in intestinal organoid development. Nature 569, 66\u201372 (2019).","journal-title":"Nature"},{"key":"1242_CR94","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1016\/j.stem.2021.04.002","volume":"28","author":"NP Tallapragada","year":"2021","unstructured":"Tallapragada, N. P. et al. Inflation-collapse dynamics drive patterning and morphogenesis in intestinal organoids. Cell Stem Cell 28, 1516\u20131532.e1514 (2021).","journal-title":"Cell Stem Cell"},{"key":"1242_CR95","doi-asserted-by":"publisher","first-page":"eadj7615","DOI":"10.1126\/science.adj7615","volume":"386","author":"MB Baghdadi","year":"2024","unstructured":"Baghdadi, M. B. et al. PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance. Science 386, eadj7615 (2024).","journal-title":"Science"},{"key":"1242_CR96","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41586-023-05915-x","volume":"619","author":"JW Hickey","year":"2023","unstructured":"Hickey, J. W. et al. Organization of the human intestine at single-cell resolution. Nature 619, 572\u2013584 (2023).","journal-title":"Nature"},{"key":"1242_CR97","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/s41556-023-01337-z","volume":"26","author":"RK Zwick","year":"2024","unstructured":"Zwick, R. K. et al. Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains. Nat. Cell Biol. 26, 250\u2013262 (2024).","journal-title":"Nat. Cell Biol."},{"key":"1242_CR98","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.cell.2018.08.067","volume":"175","author":"J Kinchen","year":"2018","unstructured":"Kinchen, J. et al. Structural remodeling of the human colonic mesenchyme in inflammatory bowel disease. Cell 175, 372\u2013386.e317 (2018).","journal-title":"Cell"},{"key":"1242_CR99","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.stem.2020.11.008","volume":"28","author":"EM Holloway","year":"2021","unstructured":"Holloway, E. M. et al. Mapping development of the human intestinal niche at single-cell resolution. Cell Stem Cell 28, 568\u2013580 e564 (2021).","journal-title":"Cell Stem Cell"},{"key":"1242_CR100","doi-asserted-by":"publisher","first-page":"685665","DOI":"10.3389\/fcell.2021.685665","volume":"9","author":"HE Abud","year":"2021","unstructured":"Abud, H. E., Chan, W. H. & Jarde, T. Source and impact of the EGF family of ligands on intestinal stem cells. Front. Cell Dev. Biol. 9, 685665 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"1242_CR101","doi-asserted-by":"publisher","first-page":"dmm049692","DOI":"10.1242\/dmm.049692","volume":"16","author":"TT Lemmetyinen","year":"2023","unstructured":"Lemmetyinen, T. T. et al. Fibroblast-derived EGF ligand neuregulin 1 induces fetal-like reprogramming of the intestinal epithelium without supporting tumorigenic growth. Dis. Model. Mech. 16, dmm049692 https:\/\/doi.org\/10.1242\/dmm.049692 (2023).","journal-title":"Dis. Model. Mech."},{"key":"1242_CR102","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.cell.2020.12.016","volume":"184","author":"D Fawkner-Corbett","year":"2021","unstructured":"Fawkner-Corbett, D. et al. Spatiotemporal analysis of human intestinal development at single-cell resolution. Cell 184, 810\u2013826.e823 (2021).","journal-title":"Cell"},{"key":"1242_CR103","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.stem.2025.02.007","volume":"32","author":"CJ Childs","year":"2025","unstructured":"Childs, C. J. et al. Coordinated differentiation of human intestinal organoids with functional enteric neurons and vasculature. Cell Stem Cell 32, 640\u2013651.e649 (2025).","journal-title":"Cell Stem Cell"},{"key":"1242_CR104","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/s41551-024-01313-4","volume":"9","author":"M Hofer","year":"2025","unstructured":"Hofer, M., Duque-Correa, M. A. & Lutolf, M. P. Patterned gastrointestinal monolayers with bilateral access as observable models of parasite gut infection. Nat. Biomed. Eng. 9, 1075\u20131085 (2025).","journal-title":"Nat. Biomed. Eng."},{"key":"1242_CR105","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.jcmgh.2021.12.005","volume":"13","author":"AR Meyer","year":"2022","unstructured":"Meyer, A. R., Brown, M. E., McGrath, P. S. & Dempsey, P. J. Injury-induced cellular plasticity drives intestinal regeneration. Cell. Mol. Gastroenterol. Hepatol. 13, 843\u2013856 (2022).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR106","doi-asserted-by":"publisher","first-page":"111796","DOI":"10.1016\/j.celrep.2022.111796","volume":"41","author":"XT Huang","year":"2022","unstructured":"Huang, X. T. et al. Embryogenic stem cell-derived intestinal crypt fission directs de novo crypt genesis. Cell Rep. 41, 111796 (2022).","journal-title":"Cell Rep."},{"key":"1242_CR107","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.jcmgh.2019.04.001","volume":"8","author":"KH Kaestner","year":"2019","unstructured":"Kaestner, K. H. The intestinal stem cell niche: a central role for foxl1-expressing subepithelial telocytes. Cell. Mol. Gastroenterol. Hepatol. 8, 111\u2013117 (2019).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR108","doi-asserted-by":"publisher","first-page":"104755","DOI":"10.1016\/j.jprot.2022.104755","volume":"271","author":"V Pomerleau","year":"2023","unstructured":"Pomerleau, V. et al. FOXL1+ telocytes in mouse colon orchestrate extracellular matrix biodynamics and wound repair resolution. J. Proteom. 271, 104755 (2023).","journal-title":"J. Proteom."},{"key":"1242_CR109","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1016\/j.stem.2023.07.013","volume":"30","author":"P Wang","year":"2023","unstructured":"Wang, P. et al. Adrenergic nerves regulate intestinal regeneration through IL-22 signaling from type 3 innate lymphoid cells. Cell Stem Cell 30, 1166\u20131178.e1168 (2023).","journal-title":"Cell Stem Cell"},{"key":"1242_CR110","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1016\/j.stem.2021.08.007","volume":"28","author":"S Beyaz","year":"2021","unstructured":"Beyaz, S. et al. Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis. Cell Stem Cell 28, 1922\u20131935.e1925 (2021).","journal-title":"Cell Stem Cell"},{"key":"1242_CR111","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s12276-024-01179-1","volume":"56","author":"J Choi","year":"2024","unstructured":"Choi, J. & Augenlicht, L. H. Intestinal stem cells: guardians of homeostasis in health and aging amid environmental challenges. Exp. Mol. Med. 56, 495\u2013500 (2024).","journal-title":"Exp. Mol. Med."},{"key":"1242_CR112","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1073\/pnas.1013004108","volume":"108","author":"RK Montgomery","year":"2011","unstructured":"Montgomery, R. K. et al. Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc. Natl Acad. Sci. USA 108, 179\u2013184 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR113","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.cell.2012.02.042","volume":"149","author":"AE Powell","year":"2012","unstructured":"Powell, A. E. et al. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 149, 146\u2013158 (2012).","journal-title":"Cell"},{"key":"1242_CR114","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1083\/jcb.201604119","volume":"215","author":"M Yousefi","year":"2016","unstructured":"Yousefi, M. et al. Msi RNA-binding proteins control reserve intestinal stem cell quiescence. J. Cell Biol. 215, 401\u2013413 (2016).","journal-title":"J. Cell Biol."},{"key":"1242_CR115","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.stem.2018.07.002","volume":"23","author":"G Tomic","year":"2018","unstructured":"Tomic, G. et al. Phospho-regulation of ATOH1 is required for plasticity of secretory progenitors and tissue regeneration. Cell Stem Cell 23, 436\u2013443.e437 (2018).","journal-title":"Cell Stem Cell"},{"key":"1242_CR116","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.stem.2017.06.014","volume":"21","author":"KS Yan","year":"2017","unstructured":"Yan, K. S. et al. Intestinal enteroendocrine lineage cells possess homeostatic and injury-inducible stem cell activity. Cell Stem Cell 21, 78\u201390.e76 (2017).","journal-title":"Cell Stem Cell"},{"key":"1242_CR117","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1172\/JCI73434","volume":"124","author":"CB Westphalen","year":"2014","unstructured":"Westphalen, C. B. et al. Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J. Clin. Invest. 124, 1283\u20131295 (2014).","journal-title":"J. Clin. Invest."},{"key":"1242_CR118","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.jcmgh.2018.11.004","volume":"7","author":"JC Jones","year":"2019","unstructured":"Jones, J. C. et al. Cellular plasticity of Defa4Cre-expressing Paneth cells in response to notch activation and intestinal injury. Cell. Mol. Gastroenterol. Hepatol. 7, 533\u2013554 (2019).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR119","doi-asserted-by":"publisher","first-page":"4368","DOI":"10.1038\/s41467-019-12349-5","volume":"10","author":"C Harnack","year":"2019","unstructured":"Harnack, C. et al. R-spondin 3 promotes stem cell recovery and epithelial regeneration in the colon. Nat. Commun. 10, 4368 (2019).","journal-title":"Nat. Commun."},{"key":"1242_CR120","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1126\/science.1112521","volume":"309","author":"KA Kim","year":"2005","unstructured":"Kim, K. A. et al. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309, 1256\u20131259 (2005).","journal-title":"Science"},{"key":"1242_CR121","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1053\/j.gastro.2007.02.001","volume":"132","author":"J Zhao","year":"2007","unstructured":"Zhao, J. et al. R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice. Gastroenterology 132, 1331\u20131343 (2007).","journal-title":"Gastroenterology"},{"key":"1242_CR122","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/nature12416","volume":"501","author":"WJ Zhou","year":"2013","unstructured":"Zhou, W. J., Geng, Z. H., Spence, J. R. & Geng, J. G. Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection. Nature 501, 107\u2013111 (2013).","journal-title":"Nature"},{"key":"1242_CR123","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature14228","volume":"519","author":"K Taniguchi","year":"2015","unstructured":"Taniguchi, K. et al. A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature 519, 57\u201362 (2015).","journal-title":"Nature"},{"key":"1242_CR124","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nature09637","volume":"469","author":"T Sato","year":"2011","unstructured":"Sato, T. et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469, 415\u2013418 (2011).","journal-title":"Nature"},{"key":"1242_CR125","doi-asserted-by":"publisher","first-page":"2312","DOI":"10.1016\/j.celrep.2018.07.085","volume":"24","author":"M Schmitt","year":"2018","unstructured":"Schmitt, M. et al. Paneth cells respond to inflammation and contribute to tissue regeneration by acquiring stem-like features through SCF\/c-kit signaling. Cell Rep. 24, 2312\u20132328.e2317 (2018).","journal-title":"Cell Rep."},{"key":"1242_CR126","doi-asserted-by":"publisher","first-page":"8965","DOI":"10.1073\/pnas.1201652109","volume":"109","author":"A Durand","year":"2012","unstructured":"Durand, A. et al. Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1). Proc. Natl Acad. Sci. USA 109, 8965\u20138970 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR127","doi-asserted-by":"publisher","first-page":"26599","DOI":"10.1073\/pnas.1801888117","volume":"116","author":"JH van Es","year":"2019","unstructured":"van Es, J. H. et al. Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion. Proc. Natl Acad. Sci. USA 116, 26599\u201326605 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR128","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.cell.2014.03.055","volume":"157","author":"RR Chivukula","year":"2014","unstructured":"Chivukula, R. R. et al. An essential mesenchymal function for miR-143\/145 in intestinal epithelial regeneration. Cell 157, 1104\u20131116 (2014).","journal-title":"Cell"},{"key":"1242_CR129","doi-asserted-by":"publisher","first-page":"409","DOI":"10.15252\/embj.201695690","volume":"36","author":"H Horiguchi","year":"2017","unstructured":"Horiguchi, H. et al. ANGPTL2 expression in the intestinal stem cell niche controls epithelial regeneration and homeostasis. EMBO J. 36, 409\u2013424 (2017).","journal-title":"EMBO J."},{"key":"1242_CR130","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/s41586-018-0190-3","volume":"558","author":"B Degirmenci","year":"2018","unstructured":"Degirmenci, B., Valenta, T., Dimitrieva, S., Hausmann, G. & Basler, K. GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells. Nature 558, 449\u2013453 (2018).","journal-title":"Nature"},{"key":"1242_CR131","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1172\/JCI29159","volume":"117","author":"SL Brown","year":"2007","unstructured":"Brown, S. L. et al. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J. Clin. Invest. 117, 258\u2013269 (2007).","journal-title":"J. Clin. Invest."},{"key":"1242_CR132","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/s41586-021-03283-y","volume":"592","author":"N Wu","year":"2021","unstructured":"Wu, N. et al. MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche. Nature 592, 606\u2013610 (2021).","journal-title":"Nature"},{"key":"1242_CR133","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1073\/pnas.0405979102","volume":"102","author":"SL Pull","year":"2005","unstructured":"Pull, S. L., Doherty, J. M., Mills, J. C., Gordon, J. I. & Stappenbeck, T. S. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc. Natl Acad. Sci. USA 102, 99\u2013104 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR134","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1084\/jem.20150318","volume":"212","author":"P Aparicio-Domingo","year":"2015","unstructured":"Aparicio-Domingo, P. et al. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage. J. Exp. Med. 212, 1783\u20131791 (2015).","journal-title":"J. Exp. Med."},{"key":"1242_CR135","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.immuni.2012.05.028","volume":"37","author":"AM Hanash","year":"2012","unstructured":"Hanash, A. M. et al. Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. Immunity 37, 339\u2013350 (2012).","journal-title":"Immunity"},{"key":"1242_CR136","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/nature16460","volume":"528","author":"CA Lindemans","year":"2015","unstructured":"Lindemans, C. A. et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 528, 560\u2013564 (2015).","journal-title":"Nature"},{"key":"1242_CR137","doi-asserted-by":"publisher","first-page":"37296","DOI":"10.1074\/jbc.M112.375881","volume":"287","author":"MD Neal","year":"2012","unstructured":"Neal, M. D. et al. Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis. J. Biol. Chem. 287, 37296\u201337308 (2012).","journal-title":"J. Biol. Chem."},{"key":"1242_CR138","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1073\/pnas.1902788117","volume":"117","author":"A Levy","year":"2020","unstructured":"Levy, A. et al. Innate immune receptor NOD2 mediates LGR5+ intestinal stem cell protection against ROS cytotoxicity via mitophagy stimulation. Proc. Natl Acad. Sci. USA 117, 1994\u20132003 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1242_CR139","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1053\/j.gastro.2006.11.022","volume":"132","author":"F Yan","year":"2007","unstructured":"Yan, F. et al. Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology 132, 562\u2013575 (2007).","journal-title":"Gastroenterology"},{"key":"1242_CR140","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.chom.2018.11.002","volume":"24","author":"YS Lee","year":"2018","unstructured":"Lee, Y. S. et al. Microbiota-derived lactate accelerates intestinal stem-cell-mediated epithelial development. Cell Host Microbe 24, 833\u2013846.e836 (2018).","journal-title":"Cell Host Microbe"},{"key":"1242_CR141","doi-asserted-by":"publisher","first-page":"115438","DOI":"10.1016\/j.celrep.2025.115438","volume":"44","author":"KS Mears","year":"2025","unstructured":"Mears, K. S. et al. Therapeutic activation of IL-22-producing innate lymphoid cells enhances host defenses to Clostridioides difficile infection. Cell Rep. 44, 115438 (2025).","journal-title":"Cell Rep."},{"key":"1242_CR142","doi-asserted-by":"publisher","first-page":"G262","DOI":"10.1152\/ajpgi.00251.2022","volume":"324","author":"MT Ok","year":"2023","unstructured":"Ok, M. T. et al. A leaky human colon model reveals uncoupled apical\/basal cytotoxicity in early Clostridioides difficile toxin exposure. Am. J. Physiol. Gastrointest. Liver Physiol. 324, G262\u2013G280 (2023).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol"},{"key":"1242_CR143","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1053\/j.gastro.2013.04.050","volume":"145","author":"F Wang","year":"2013","unstructured":"Wang, F. et al. Isolation and characterization of intestinal stem cells based on surface marker combinations and colony-formation assay. Gastroenterology 145, 383\u2013395.e381-321 (2013).","journal-title":"Gastroenterology"},{"key":"1242_CR144","doi-asserted-by":"publisher","first-page":"G252","DOI":"10.1152\/ajpgi.00203.2024","volume":"328","author":"G Al-Qadami","year":"2025","unstructured":"Al-Qadami, G. et al. Intestinal organoid coculture systems: current approaches, challenges, and future directions. Am. J. Physiol. Gastrointest. Liver Physiol. 328, G252\u2013G276 (2025).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"1242_CR145","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1016\/j.cell.2018.11.021","volume":"175","author":"JT Neal","year":"2018","unstructured":"Neal, J. T. et al. Organoid modeling of the tumor immune microenvironment. Cell 175, 1972\u20131988.e1916 (2018).","journal-title":"Cell"},{"key":"1242_CR146","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/nm.3585","volume":"20","author":"X Li","year":"2014","unstructured":"Li, X. et al. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat. Med. 20, 769\u2013777 (2014).","journal-title":"Nat. Med."},{"key":"1242_CR147","doi-asserted-by":"publisher","DOI":"10.3791\/54344","author":"HJ Kim","year":"2016","unstructured":"Kim, H. J., Lee, J., Choi, J. H., Bahinski, A. & Ingber, D. E. Co-culture of living microbiome with microengineered human intestinal villi in a gut-on-a-chip microfluidic device. J. Vis. Exp. https:\/\/doi.org\/10.3791\/54344 (2016).","journal-title":"J. Vis. Exp."},{"key":"1242_CR148","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/s41551-019-0397-0","volume":"3","author":"S Jalili-Firoozinezhad","year":"2019","unstructured":"Jalili-Firoozinezhad, S. et al. A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip. Nat. Biomed. Eng. 3, 520\u2013531 (2019).","journal-title":"Nat. Biomed. Eng."},{"key":"1242_CR149","doi-asserted-by":"publisher","first-page":"2886","DOI":"10.1002\/bit.27816","volume":"118","author":"L Sardelli","year":"2021","unstructured":"Sardelli, L. et al. Technological tools and strategies for culturing human gut microbiota in engineered in vitro models. Biotechnol. Bioeng. 118, 2886\u20132905 (2021).","journal-title":"Biotechnol. Bioeng."},{"key":"1242_CR150","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41563-020-00803-5","volume":"20","author":"JA Brassard","year":"2021","unstructured":"Brassard, J. A., Nikolaev, M., Hubscher, T., Hofer, M. & Lutolf, M. P. Recapitulating macro-scale tissue self-organization through organoid bioprinting. Nat. Mater. 20, 22\u201329 (2021).","journal-title":"Nat. Mater."},{"key":"1242_CR151","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50135","volume":"9","author":"M Kasendra","year":"2020","unstructured":"Kasendra, M. et al. Duodenum intestine-chip for preclinical drug assessment in a human relevant model. eLife 9, e50135 (2020).","journal-title":"eLife"},{"key":"1242_CR152","doi-asserted-by":"publisher","first-page":"120957","DOI":"10.1016\/j.biomaterials.2021.120957","volume":"275","author":"A Varone","year":"2021","unstructured":"Varone, A. et al. A novel organ-chip system emulates three-dimensional architecture of the human epithelia and the mechanical forces acting on it. Biomaterials 275, 120957 (2021).","journal-title":"Biomaterials"},{"key":"1242_CR153","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41586-025-08808-3","volume":"642","author":"JI Kim","year":"2025","unstructured":"Kim, J. I. et al. Human assembloid model of the ascending neural sensory pathway. Nature 642, 143\u2013153 (2025).","journal-title":"Nature"},{"key":"1242_CR154","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33844-2","volume":"13","author":"A Fazio","year":"2022","unstructured":"Fazio, A. et al. DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon. Nat. Commun. 13, 6266 (2022).","journal-title":"Nat. Commun."},{"key":"1242_CR155","doi-asserted-by":"publisher","first-page":"101774","DOI":"10.1016\/j.jcmgh.2026.101774","volume":"20","author":"FH Hamdan","year":"2026","unstructured":"Hamdan, F. H. et al. Intestinal stem cells from patients with inflammatory bowel disease retain an epigenetic memory of inflammation. Cell. Mol. Gastroenterol. Hepatol. 20, 101774 https:\/\/doi.org\/10.1016\/j.jcmgh.2026.101774 (2026).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR156","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1053\/j.gastro.2017.10.007","volume":"154","author":"KJ Howell","year":"2018","unstructured":"Howell, K. J. et al. DNA methylation and transcription patterns in intestinal epithelial cells from pediatric patients with inflammatory bowel diseases differentiate disease subtypes and associate with outcome. Gastroenterology 154, 585\u2013598 (2018).","journal-title":"Gastroenterology"},{"key":"1242_CR157","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1016\/j.jcmgh.2021.06.018","volume":"12","author":"BJ Niklinska-Schirtz","year":"2021","unstructured":"Niklinska-Schirtz, B. J. et al. Ileal derived organoids from crohn\u2019s disease patients show unique transcriptomic and secretomic signatures. Cell. Mol. Gastroenterol. Hepatol. 12, 1267\u20131280 (2021).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR158","doi-asserted-by":"publisher","first-page":"28717","DOI":"10.18632\/oncotarget.25617","volume":"9","author":"SK Sarvestani","year":"2018","unstructured":"Sarvestani, S. K. et al. Cancer-predicting transcriptomic and epigenetic signatures revealed for ulcerative colitis in patient-derived epithelial organoids. Oncotarget 9, 28717\u201328730 (2018).","journal-title":"Oncotarget"},{"key":"1242_CR159","doi-asserted-by":"publisher","first-page":"367","DOI":"10.15252\/embr.201643732","volume":"18","author":"J Nie","year":"2017","unstructured":"Nie, J. & Hashino, E. Organoid technologies meet genome engineering. EMBO Rep. 18, 367\u2013376 (2017).","journal-title":"EMBO Rep."},{"key":"1242_CR160","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40701-3","volume":"14","author":"MH Geurts","year":"2023","unstructured":"Geurts, M. H. et al. One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids. Nat. Commun. 14, 4998 (2023).","journal-title":"Nat. Commun."},{"key":"1242_CR161","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1038\/nprot.2015.088","volume":"10","author":"M Fujii","year":"2015","unstructured":"Fujii, M., Matano, M., Nanki, K. & Sato, T. Efficient genetic engineering of human intestinal organoids using electroporation. Nat. Protoc. 10, 1474\u20131485 (2015).","journal-title":"Nat. Protoc."},{"key":"1242_CR162","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1038\/s41587-025-02830-6","volume":"44","author":"AC Daly","year":"2025","unstructured":"Daly, A. C. et al. Tissue and cellular spatiotemporal dynamics in colon aging. Nat. Biotechnol. 44, 1340\u20131352 https:\/\/doi.org\/10.1038\/s41587-025-02830-6 (2025).","journal-title":"Nat. Biotechnol."},{"key":"1242_CR163","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/s41586-024-07793-3","volume":"632","author":"Y Harnik","year":"2024","unstructured":"Harnik, Y. et al. A spatial expression atlas of the adult human proximal small intestine. Nature 632, 1101\u20131109 (2024).","journal-title":"Nature"},{"key":"1242_CR164","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/s41586-025-09744-y","volume":"649","author":"C McGregor","year":"2025","unstructured":"McGregor, C. et al. Spatial fibroblast niches define Crohn\u2019s fistulae. Nature 649, 703\u2013712\u00a0https:\/\/doi.org\/10.1038\/s41586-025-09744-y (2025).","journal-title":"Nature"},{"key":"1242_CR165","doi-asserted-by":"publisher","unstructured":"Ofer, R. et al. A spatial and temporal transcriptomic atlas of mouse intestinal regeneration. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.08.06.668727 (2025).","DOI":"10.1101\/2025.08.06.668727"},{"issue":"Suppl 1","key":"1242_CR166","first-page":"S98","volume":"38","author":"C Belza","year":"2023","unstructured":"Belza, C. & Wales, P. W. Intestinal failure among adults and children: similarities and differences. Nutr. Clin. Pract. 38 (Suppl. 1), S98\u2013S113 (2023).","journal-title":"Nutr. Clin. Pract."},{"key":"1242_CR167","doi-asserted-by":"publisher","first-page":"151175","DOI":"10.1016\/j.sempedsurg.2022.151175","volume":"31","author":"C Belza","year":"2022","unstructured":"Belza, C. & Wales, P. W. Management of pediatric intestinal failure related to short bowel syndrome. Semin. Pediatr. Surg. 31, 151175 (2022).","journal-title":"Semin. Pediatr. Surg."},{"key":"1242_CR168","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237885","volume":"15","author":"A Singh","year":"2020","unstructured":"Singh, A. et al. Evaluation of transplantation sites for human intestinal organoids. PLoS ONE 15, e0237885 (2020).","journal-title":"PLoS ONE"},{"key":"1242_CR169","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/j.stem.2024.08.009","volume":"31","author":"HM Poling","year":"2024","unstructured":"Poling, H. M. et al. Human pluripotent stem cell-derived organoids repair damaged bowel in vivo. Cell Stem Cell 31, 1513\u20131523.e1517 (2024).","journal-title":"Cell Stem Cell"},{"key":"1242_CR170","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.stem.2017.11.012","volume":"22","author":"S Sugimoto","year":"2018","unstructured":"Sugimoto, S. et al. Reconstruction of the human colon epithelium in vivo. Cell Stem Cell 22, 171\u2013176.e175 (2018).","journal-title":"Cell Stem Cell"},{"key":"1242_CR171","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1038\/s41563-025-02241-7","volume":"24","author":"X Gong","year":"2025","unstructured":"Gong, X. et al. Instant assembly of collagen for tissue engineering and bioprinting. Nat. Mater. 24, 1307\u20131318 (2025).","journal-title":"Nat. Mater."},{"key":"1242_CR172","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1038\/s41591-020-1024-z","volume":"26","author":"L Meran","year":"2020","unstructured":"Meran, L. et al. Engineering transplantable jejunal mucosal grafts using patient-derived organoids from children with intestinal failure. Nat. Med. 26, 1593\u20131601 (2020).","journal-title":"Nat. Med."},{"key":"1242_CR173","doi-asserted-by":"publisher","first-page":"100930","DOI":"10.1016\/j.crmeth.2024.100930","volume":"4","author":"J Takahashi","year":"2024","unstructured":"Takahashi, J. et al. Controlled aggregative assembly to form self-organizing macroscopic human intestine from induced pluripotent stem cells. Cell Rep. Methods 4, 100930 (2024).","journal-title":"Cell Rep. Methods"},{"key":"1242_CR174","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/s41586-024-07330-2","volume":"629","author":"LF Lorenzo-Mart\u00edn","year":"2024","unstructured":"Lorenzo-Mart\u00edn, L. F. et al. Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo. Nature 629, 450\u2013457 (2024).","journal-title":"Nature"},{"key":"1242_CR175","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s12015-019-09935-x","volume":"16","author":"G Liu","year":"2020","unstructured":"Liu, G., David, B. T., Trawczynski, M. & Fessler, R. G. Advances in pluripotent stem cells: history, mechanisms, technologies, and applications. Stem Cell Rev. Rep. 16, 3\u201332 (2020).","journal-title":"Stem Cell Rev. Rep."},{"key":"1242_CR176","doi-asserted-by":"publisher","first-page":"1892","DOI":"10.1136\/gutjnl-2021-326560","volume":"71","author":"C Gunther","year":"2022","unstructured":"Gunther, C., Winner, B., Neurath, M. F. & Stappenbeck, T. S. Organoids in gastrointestinal diseases: from experimental models to clinical translation. Gut 71, 1892\u20131908 (2022).","journal-title":"Gut"},{"key":"1242_CR177","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/MOG.0000000000000691","volume":"37","author":"R Dheer","year":"2021","unstructured":"Dheer, R. & Young, V. B. Stem-cell-derived models: tools for studying role of microbiota in intestinal homeostasis and disease. Curr. Opin. Gastroenterol. 37, 15\u201322 (2021).","journal-title":"Curr. Opin. Gastroenterol."},{"key":"1242_CR178","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1056\/NEJMoa1608368","volume":"376","author":"M Mandai","year":"2017","unstructured":"Mandai, M. et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N. Engl. J. Med. 376, 1038\u20131046 (2017).","journal-title":"N. Engl. J. Med."},{"key":"1242_CR179","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.stem.2024.12.005","volume":"32","author":"A Kirkeby","year":"2025","unstructured":"Kirkeby, A., Main, H. & Carpenter, M. Pluripotent stem-cell-derived therapies in clinical trial: a 2025 update. Cell Stem Cell 32, 10\u201337 (2025).","journal-title":"Cell Stem Cell"},{"key":"1242_CR180","doi-asserted-by":"publisher","first-page":"750","DOI":"10.5966\/sctm.2012-0072","volume":"1","author":"LG Chase","year":"2012","unstructured":"Chase, L. G. et al. Development and characterization of a clinically compliant xeno-free culture medium in good manufacturing practice for human multipotent mesenchymal stem cells. Stem Cell Transl. Med. 1, 750\u2013758 (2012).","journal-title":"Stem Cell Transl. Med."},{"key":"1242_CR181","doi-asserted-by":"publisher","first-page":"662360","DOI":"10.3389\/fimmu.2021.662360","volume":"12","author":"C Flahou","year":"2021","unstructured":"Flahou, C., Morishima, T., Takizawa, H. & Sugimoto, N. Fit-for-all iPSC-derived cell therapies and their evaluation in humanized mice with NK cell immunity. Front. Immunol. 12, 662360 (2021).","journal-title":"Front. Immunol."},{"key":"1242_CR182","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1152\/ajpgi.00425.2020","volume":"321","author":"M Kasendra","year":"2021","unstructured":"Kasendra, M. et al. Intestinal organoids: roadmap to the clinic. Am. J. Physiol. Gastrointest. Liver Physiol. 321, G1\u2013G10 (2021).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol"},{"key":"1242_CR183","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1056\/NEJMoa2506549","volume":"393","author":"TW Reichman","year":"2025","unstructured":"Reichman, T. W. et al. Stem cell-derived, fully differentiated islets for type 1 diabetes. N. Engl. J. Med. 393, 858\u2013868 https:\/\/doi.org\/10.1056\/NEJMoa2506549 (2025).","journal-title":"N. Engl. J. Med."},{"key":"1242_CR184","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1007\/s12015-025-10893-w","volume":"21","author":"D Kumar","year":"2025","unstructured":"Kumar, D., Gupta, S., Gupta, V., Tanwar, R. & Chandel, A. Engineering the future of regenerative medicines in gut health with stem cell-derived intestinal organoids. Stem Cell Rev. Rep. 21, 1449\u20131470 (2025).","journal-title":"Stem Cell Rev. Rep."},{"key":"1242_CR185","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.stem.2025.12.007","volume":"33","author":"R Endo","year":"2026","unstructured":"Endo, R. et al. Niche-preserving transplantation promotes functional engraftment of intestinal organoids in rat short bowel syndrome. Cell Stem Cell 33, 157\u2013165.e156 (2026).","journal-title":"Cell Stem Cell"},{"key":"1242_CR186","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.1016\/j.devcel.2025.06.026","volume":"60","author":"A Chrisnandy","year":"2025","unstructured":"Chrisnandy, A. & Lutolf, M. P. An extracellular matrix niche secreted by epithelial cells drives intestinal organoid formation. Dev. Cell 60, 3116\u20133130.e3118 (2025).","journal-title":"Dev. Cell"},{"key":"1242_CR187","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nature22306","volume":"545","author":"CY Janda","year":"2017","unstructured":"Janda, C. Y. et al. Surrogate Wnt agonists that phenocopy canonical Wnt and \u03b2-catenin signalling. Nature 545, 234\u2013237 (2017).","journal-title":"Nature"},{"key":"1242_CR188","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.stem.2020.07.020","volume":"27","author":"Y Miao","year":"2020","unstructured":"Miao, Y. et al. Next-generation surrogate wnts support organoid growth and deconvolute frizzled pleiotropy in vivo. Cell Stem Cell 27, 840\u2013851.e846 (2020).","journal-title":"Cell Stem Cell"},{"key":"1242_CR189","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.jcmgh.2022.05.003","volume":"14","author":"L Xie","year":"2022","unstructured":"Xie, L. et al. Robust colonic epithelial regeneration and amelioration of colitis via FZD-specific activation of Wnt signaling. Cell. Mol. Gastroenterol. Hepatol. 14, 435\u2013464 (2022).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR190","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.devcel.2024.10.022","volume":"60","author":"Q Mu","year":"2025","unstructured":"Mu, Q. et al. FZD5 controls intestinal crypt homeostasis and colonic Wnt surrogate agonist response. Dev. Cell 60, 342\u2013351.e345 (2025).","journal-title":"Dev. Cell"},{"key":"1242_CR191","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.immuni.2021.03.008","volume":"54","author":"RA Saxton","year":"2021","unstructured":"Saxton, R. A. et al. The tissue protective functions of interleukin-22 can be decoupled from pro-inflammatory actions through structure-based design. Immunity 54, 660\u2013672.e669 (2021).","journal-title":"Immunity"},{"key":"1242_CR192","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1097\/MOG.0000000000001169","volume":"42","author":"L Gorard","year":"2026","unstructured":"Gorard, L., Boucher, M. & Rutter, C. Glucagon-like peptide agonists and use in short bowel syndrome\u2014what about the side effects? Curr. Opin. Gastroenterol. 42, 201\u2013207 (2026).","journal-title":"Curr. Opin. Gastroenterol."},{"key":"1242_CR193","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.cmet.2015.02.005","volume":"21","author":"JA Koehler","year":"2015","unstructured":"Koehler, J. A. et al. GLP-1R agonists promote normal and neoplastic intestinal growth through mechanisms requiring Fgf7. Cell Metab. 21, 379\u2013391 (2015).","journal-title":"Cell Metab."},{"key":"1242_CR194","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.3390\/microorganisms10102061","volume":"10","author":"N Abdalqadir","year":"2022","unstructured":"Abdalqadir, N. & Adeli, K. GLP-1 and GLP-2 orchestrate intestine integrity, gut microbiota, and immune system crosstalk. Microorganisms 10, 2061 https:\/\/doi.org\/10.3390\/microorganisms10102061 (2022).","journal-title":"Microorganisms"},{"key":"1242_CR195","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1182\/blood.2020005957","volume":"136","author":"J Norona","year":"2020","unstructured":"Norona, J. et al. Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. Blood 136, 1442\u20131455 (2020).","journal-title":"Blood"},{"key":"1242_CR196","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12876-023-02716-4","volume":"23","author":"J Skarbaliene","year":"2023","unstructured":"Skarbaliene, J., Mathiesen, J. M., Larsen, B. D., Thorkildsen, C. & Petersen, Y. M. Glepaglutide, a novel glucagon-like peptide-2 agonist, has anti-inflammatory and mucosal regenerative effects in an experimental model of inflammatory bowel disease in rats. BMC Gastroenterol. 23, 79 (2023).","journal-title":"BMC Gastroenterol."},{"key":"1242_CR197","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1016\/j.jcmgh.2022.02.011","volume":"13","author":"ME Chen","year":"2022","unstructured":"Chen, M. E. et al. Glucagon-like peptide-2 stimulates S-phase entry of intestinal Lgr5+ stem cells. Cell. Mol. Gastroenterol. Hepatol. 13, 1829\u20131842 (2022).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR198","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s13287-015-0145-7","volume":"6","author":"T O\u2019Brien","year":"2015","unstructured":"O\u2019Brien, T., Creane, M., Windebank, A. J., Terzic, A. & Dietz, A. B. Translating stem cell research to the clinic: a primer on translational considerations for your first stem cell protocol. Stem Cell Res. Ther. 6, 146 (2015).","journal-title":"Stem Cell Res. Ther."},{"key":"1242_CR199","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.stem.2017.05.020","volume":"21","author":"JO Munera","year":"2017","unstructured":"Munera, J. O. et al. Differentiation of human pluripotent stem cells into colonic organoids via transient activation of BMP signaling. Cell Stem Cell 21, 51\u201364.e56 (2017).","journal-title":"Cell Stem Cell"},{"key":"1242_CR200","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nm.4233","volume":"23","author":"MJ Workman","year":"2017","unstructured":"Workman, M. J. et al. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat. Med. 23, 49\u201359 (2017).","journal-title":"Nat. Med."},{"key":"1242_CR201","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.jcyt.2014.10.008","volume":"17","author":"S Ouseph","year":"2015","unstructured":"Ouseph, S. et al. Cellular therapies clinical research roadmap: lessons learned on how to move a cellular therapy into a clinical trial. Cytotherapy 17, 339\u2013343 (2015).","journal-title":"Cytotherapy"},{"key":"1242_CR202","doi-asserted-by":"publisher","first-page":"G461","DOI":"10.1152\/ajpgi.90446.2008","volume":"297","author":"CM Dekaney","year":"2009","unstructured":"Dekaney, C. M., Gulati, A. S., Garrison, A. P., Helmrath, M. A. & Henning, S. J. Regeneration of intestinal stem\/progenitor cells following doxorubicin treatment of mice. Am. J. Physiol. Gastrointest. Liver Physiol. 297, G461\u2013G470 (2009).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"1242_CR203","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.stem.2013.11.008","volume":"14","author":"C Metcalfe","year":"2014","unstructured":"Metcalfe, C., Kljavin, N. M., Ybarra, R. & de Sauvage, F. J. Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell 14, 149\u2013159 (2014).","journal-title":"Cell Stem Cell"},{"key":"1242_CR204","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1053\/j.gastro.2012.07.106","volume":"143","author":"G Hua","year":"2012","unstructured":"Hua, G. et al. Crypt base columnar stem cells in small intestines of mice are radioresistant. Gastroenterology 143, 1266\u20131276 (2012).","journal-title":"Gastroenterology"},{"key":"1242_CR205","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1158\/0008-5472.CAN-15-2870","volume":"77","author":"G Hua","year":"2017","unstructured":"Hua, G. et al. Distinct levels of radioresistance in Lgr5+ colonic epithelial stem cells versus Lgr5+ small intestinal stem cells. Cancer Res. 77, 2124\u20132133 (2017).","journal-title":"Cancer Res."},{"key":"1242_CR206","doi-asserted-by":"publisher","first-page":"107952","DOI":"10.1016\/j.celrep.2020.107952","volume":"32","author":"X Sheng","year":"2020","unstructured":"Sheng, X. et al. Cycling stem cells are radioresistant and regenerate the intestine. Cell Rep. 32, 107952 (2020).","journal-title":"Cell Rep."},{"key":"1242_CR207","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1053\/j.gastro.2018.11.024","volume":"156","author":"Y Hayakawa","year":"2019","unstructured":"Hayakawa, Y. et al. BHLHA15-positive secretory precursor cells can give rise to tumors in intestine and colon in mice. Gastroenterology 156, 1066\u20131081.e1016 (2019).","journal-title":"Gastroenterology"},{"key":"1242_CR208","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1016\/j.celrep.2017.12.093","volume":"22","author":"WY Zou","year":"2018","unstructured":"Zou, W. Y. et al. Epithelial WNT ligands are essential drivers of intestinal stem cell activation. Cell Rep. 22, 1003\u20131015 (2018).","journal-title":"Cell Rep."},{"key":"1242_CR209","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3390\/ani12020175","volume":"12","author":"P Baska","year":"2022","unstructured":"Baska, P. & Norbury, L. J. The role of the intestinal epithelium in the \u201cweep and sweep\u201d response during gastro-intestinal helminth infections. Animals 12, 175 https:\/\/doi.org\/10.3390\/ani12020175 (2022).","journal-title":"Animals"},{"key":"1242_CR210","doi-asserted-by":"publisher","first-page":"e20212311","DOI":"10.1084\/jem.20212311","volume":"219","author":"D Karo-Atar","year":"2022","unstructured":"Karo-Atar, D. et al. Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity. J. Exp. Med. 219, e20212311\u00a0https:\/\/doi.org\/10.1084\/jem.20212311 (2022).","journal-title":"J. Exp. Med."},{"key":"1242_CR211","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1038\/s41385-022-00498-8","volume":"15","author":"M Moyat","year":"2022","unstructured":"Moyat, M. et al. Microbial regulation of intestinal motility provides resistance against helminth infection. Mucosal Immunol. 15, 1283\u20131295 (2022).","journal-title":"Mucosal Immunol."},{"key":"1242_CR212","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature16161","volume":"529","author":"J von Moltke","year":"2016","unstructured":"von Moltke, J., Ji, M., Liang, H. E. & Locksley, R. M. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529, 221\u2013225 (2016).","journal-title":"Nature"},{"key":"1242_CR213","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.jcmgh.2019.11.001","volume":"9","author":"AP Singh","year":"2020","unstructured":"Singh, A. P. et al. Enteroendocrine progenitor cell-enriched miR-7 regulates intestinal epithelial proliferation in an xiap-dependent manner. Cell. Mol. Gastroenterol. Hepatol. 9, 447\u2013464 (2020).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"1242_CR214","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/978-1-4939-6949-4_17","volume":"1597","author":"MM Mahe","year":"2017","unstructured":"Mahe, M. M., Brown, N. E., Poling, H. M. & Helmrath, M. A. In vivo model of small intestine. Methods Mol. Biol. 1597, 229\u2013245 (2017).","journal-title":"Methods Mol. Biol."},{"key":"1242_CR215","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.surg.2018.04.048","volume":"164","author":"AR Cortez","year":"2018","unstructured":"Cortez, A. R. et al. Transplantation of human intestinal organoids into the mouse mesentery: a more physiologic and anatomic engraftment site. Surgery 164, 643\u2013650 (2018).","journal-title":"Surgery"}],"container-title":["Nature Reviews Gastroenterology & Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41575-026-01242-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41575-026-01242-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41575-026-01242-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:02:12Z","timestamp":1788458532000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41575-026-01242-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":215,"alternative-id":["1242"],"URL":"https:\/\/doi.org\/10.1038\/s41575-026-01242-4","relation":{},"ISSN":["1759-5045","1759-5053"],"issn-type":[{"value":"1759-5045","type":"print"},{"value":"1759-5053","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"assertion":[{"value":"31 July 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2026","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.J.K. is a SAB member for Surrozen and Mozart Therapeutics. C.J.K., M.A.H. and A.J.M.S. are inventors on patents related to intestinal organoid technologies. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}