{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T07:36:21Z","timestamp":1794036981056,"version":"4.8.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["2U19AI067798"],"award-info":[{"award-number":["2U19AI067798"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["2U19AI067798"],"award-info":[{"award-number":["2U19AI067798"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI067773"],"award-info":[{"award-number":["U19AI067773"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["1P01CA257904"],"award-info":[{"award-number":["1P01CA257904"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/05p26gw61","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["2R35CA197616"],"award-info":[{"award-number":["2R35CA197616"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/05p26gw61","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["1P01CA257904"],"award-info":[{"award-number":["1P01CA257904"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/05p26gw61","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["1P01CA257904"],"award-info":[{"award-number":["1P01CA257904"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/05p26gw61","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","id":[{"id":"https:\/\/ror.org\/05p26gw61","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","id":[{"id":"https:\/\/ror.org\/05p26gw61","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014599","name":"The Mark Foundation for Cancer Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014599","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","id":[{"id":"https:\/\/ror.org\/05p26gw61","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Duke University School of Medicine Whitehead Scholar Award","id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of the irradiated mouse small intestine, we find that p53 target genes are specifically enriched in regenerating epithelial cells that undergo fetal-like reversion, including revival stem cells (revSCs) that promote animal survival after severe damage of the GI tract. Accordingly, in mice with p53 deleted specifically in the GI epithelium, ionizing radiation fails to induce fetal-like revSCs. Using intestinal organoids, we show that transient p53 expression is required for the induction of revival stem cells and is controlled by an Mdm2-mediated negative feedback loop. Together, our findings reveal that p53 suppresses severe radiation-induced GI injury by promoting fetal-like reprogramming of irradiated intestinal epithelial cells.<\/jats:p>","DOI":"10.1038\/s41467-024-47124-8","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T07:02:08Z","timestamp":1712559728000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["p53 promotes revival stem cells in the regenerating intestine after severe radiation injury"],"prefix":"10.1038","volume":"15","author":[{"given":"Clara","family":"Morral","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshad","family":"Ayyaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsuan-Cheng","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mardi","family":"Fink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis I.","family":"Verginadis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea R.","family":"Daniel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle N.","family":"Burner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8868-3242","authenticated-orcid":false,"given":"Lucy M.","family":"Driver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sloane","family":"Satow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Hasapis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Ghinnagow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1782-9045","authenticated-orcid":false,"given":"Laura D.","family":"Attardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos","family":"Koumenis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1418-0906","authenticated-orcid":false,"given":"Andy J.","family":"Minn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0932-0644","authenticated-orcid":false,"given":"Jeffrey L.","family":"Wrana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-633X","authenticated-orcid":false,"given":"Chang-Lung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2086-205X","authenticated-orcid":false,"given":"David G.","family":"Kirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,8]]},"reference":[{"key":"47124_CR1","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.7326\/0003-4819-140-12-200406150-00015","volume":"140","author":"JK Waselenko","year":"2004","unstructured":"Waselenko, J. K. et al. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann. Intern. Med. 140, 1037\u20131051 (2004).","journal-title":"Ann. Intern. Med."},{"key":"47124_CR2","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":"47124_CR3","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":"47124_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108633","volume":"34","author":"SH Tan","year":"2021","unstructured":"Tan, S. H. et al. A constant pool of Lgr5(+) intestinal stem cells is required for intestinal homeostasis. Cell Rep. 34, 108633 (2021).","journal-title":"Cell Rep."},{"key":"47124_CR5","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":"47124_CR6","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1126\/science.abb6848","volume":"371","author":"RA Shivdasani","year":"2021","unstructured":"Shivdasani, R. A., Clevers, H. & de Sauvage, F. J. Tissue regeneration: reserve or reverse? Science 371, 784\u2013786 (2021).","journal-title":"Science"},{"key":"47124_CR7","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.jcmgh.2021.01.015","volume":"12","author":"BJ Sheahan","year":"2021","unstructured":"Sheahan, B. J. et al. Epithelial regeneration after doxorubicin arises primarily from early progeny of active intestinal stem cells. Cell. Mol. Gastroenterol. Hepatol. 12, 119\u2013140 (2021).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"47124_CR8","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.stem.2019.12.011","volume":"26","author":"K. Murata","year":"2010","unstructured":"Murata, K. et al. Ascl2-dependent cell dedifferentiation drives regeneration of ablated intestinal stem cells. Cell Stem Cell 26, 377\u2013390.e6 (2020).","journal-title":"Cell Stem Cell"},{"key":"47124_CR9","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1126\/science.1166202","volume":"327","author":"DG Kirsch","year":"2010","unstructured":"Kirsch, D. G. et al. p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science 327, 593\u2013596 (2010).","journal-title":"Science"},{"key":"47124_CR10","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1016\/j.cell.2018.08.063","volume":"175","author":"AE Moor","year":"2018","unstructured":"Moor, A. E. et al. Spatial reconstruction of single enterocytes uncovers broad zonation along the intestinal villus axis. Cell 175, 1156\u20131167.e1115 (2018).","journal-title":"Cell"},{"key":"47124_CR11","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":"47124_CR12","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":"47124_CR13","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":"47124_CR14","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":"47124_CR15","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/nature15382","volume":"526","author":"A Gregorieff","year":"2015","unstructured":"Gregorieff, A., Liu, Y., Inanlou, M. R., Khomchuk, Y. & Wrana, J. L. Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer. Nature 526, 715\u2013718 (2015).","journal-title":"Nature"},{"key":"47124_CR16","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":"47124_CR17","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":"47124_CR18","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1053\/j.gastro.2009.05.035","volume":"137","author":"LG van der Flier","year":"2009","unstructured":"van der Flier, L. G., Haegebarth, A., Stange, D. E., van de Wetering, M. & Clevers, H. OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology 137, 15\u201317 (2009).","journal-title":"Gastroenterology"},{"key":"47124_CR19","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.stem.2014.12.006","volume":"16","author":"J Schuijers","year":"2015","unstructured":"Schuijers, J. et al. Ascl2 acts as an R-spondin\/Wnt-responsive switch to control stemness in intestinal crypts. Cell Stem Cell 16, 158\u2013170 (2015).","journal-title":"Cell Stem Cell"},{"key":"47124_CR20","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1016\/j.stem.2023.09.015","volume":"30","author":"L Chen","year":"2023","unstructured":"Chen, L. et al. TGFB1 induces fetal reprogramming and enhances intestinal regeneration. Cell Stem Cell 30, 1520\u20131537.e8 (2023).","journal-title":"Cell Stem Cell"},{"key":"47124_CR21","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.cell.2011.03.035","volume":"145","author":"CA Brady","year":"2011","unstructured":"Brady, C. A. et al. Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell 145, 571\u2013583 (2011).","journal-title":"Cell"},{"key":"47124_CR22","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.stem.2020.07.003","volume":"27","author":"P Cheung","year":"2020","unstructured":"Cheung, P. et al. Regenerative reprogramming of the intestinal stem cell state via hippo signaling suppresses metastatic colorectal cancer. Cell Stem Cell 27, 590\u2013604.e599 (2020).","journal-title":"Cell Stem Cell"},{"key":"47124_CR23","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1126\/science.285.5434.1733","volume":"285","author":"PG Komarov","year":"1999","unstructured":"Komarov, P. G. et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285, 1733\u20131737 (1999).","journal-title":"Science"},{"key":"47124_CR24","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1126\/science.1092472","volume":"303","author":"LT Vassilev","year":"2004","unstructured":"Vassilev, L. T. et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303, 844\u2013848 (2004).","journal-title":"Science"},{"key":"47124_CR25","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/387299a0","volume":"387","author":"MH Kubbutat","year":"1997","unstructured":"Kubbutat, M. H., Jones, S. N. & Vousden, K. H. Regulation of p53 stability by Mdm2. Nature 387, 299\u2013303 (1997).","journal-title":"Nature"},{"key":"47124_CR26","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/387296a0","volume":"387","author":"Y Haupt","year":"1997","unstructured":"Haupt, Y., Maya, R., Kazaz, A. & Oren, M. Mdm2 promotes the rapid degradation of p53. Nature 387, 296\u2013299 (1997).","journal-title":"Nature"},{"key":"47124_CR27","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1101\/gad.9.8.935","volume":"9","author":"KF Macleod","year":"1995","unstructured":"Macleod, K. F. et al. p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev. 9, 935\u2013944 (1995).","journal-title":"Genes Dev."},{"key":"47124_CR28","doi-asserted-by":"publisher","first-page":"7337","DOI":"10.1074\/jbc.275.10.7337","volume":"275","author":"M Schuler","year":"2000","unstructured":"Schuler, M., Bossy-Wetzel, E., Goldstein, J. C., Fitzgerald, P. & Green, D. R. p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release. J. Biol. Chem. 275, 7337\u20137342 (2000).","journal-title":"J. Biol. Chem."},{"key":"47124_CR29","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.1289","volume":"4","author":"J Gupta","year":"2014","unstructured":"Gupta, J. & Nebreda, A. R. Analysis of intestinal permeability in mice. Bio Protoc. 4, e1289 (2014).","journal-title":"Bio Protoc."},{"key":"47124_CR30","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1186\/s13287-020-01887-1","volume":"11","author":"A Accarie","year":"2020","unstructured":"Accarie, A. et al. Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome. Stem Cell Res. Ther. 11, 371 (2020).","journal-title":"Stem Cell Res. Ther."},{"key":"47124_CR31","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.jcmgh.2023.03.008","volume":"16","author":"Y Shimodaira","year":"2023","unstructured":"Shimodaira, Y. et al. DR3 regulates intestinal epithelial homeostasis and regeneration after intestinal barrier injury. Cell Mol. Gastroenterol. Hepatol. 16, 83\u2013105 (2023).","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"47124_CR32","doi-asserted-by":"publisher","first-page":"17429","DOI":"10.1073\/pnas.1909550116","volume":"116","author":"V Pant","year":"2019","unstructured":"Pant, V. et al. Transient enhancement of p53 activity protects from radiation-induced gastrointestinal toxicity. Proc. Natl. Acad. Sci. USA 116, 17429\u201317437 (2019).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"47124_CR33","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1158\/1541-7786.MCR-11-0052","volume":"9","author":"BJ Leibowitz","year":"2011","unstructured":"Leibowitz, B. J. et al. Uncoupling p53 functions in radiation-induced intestinal damage via PUMA and p21. Mol. Cancer Res. 9, 616\u2013625 (2011).","journal-title":"Mol. Cancer Res."},{"key":"47124_CR34","doi-asserted-by":"publisher","first-page":"3265","DOI":"10.1038\/sj.onc.1207494","volume":"23","author":"EA Komarova","year":"2004","unstructured":"Komarova, E. A. et al. Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice. Oncogene 23, 3265\u20133271 (2004).","journal-title":"Oncogene"},{"key":"47124_CR35","doi-asserted-by":"publisher","first-page":"6225","DOI":"10.1093\/emboj\/cdf595","volume":"21","author":"I Garcia-Cao","year":"2002","unstructured":"Garcia-Cao, I. et al. \u201cSuper p53\u201d mice exhibit enhanced DNA damage response, are tumor resistant and age normally. Embo J. 21, 6225\u20136235 (2002).","journal-title":"Embo J."},{"key":"47124_CR36","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1002\/gene.20042","volume":"39","author":"F el Marjou","year":"2004","unstructured":"el Marjou, F. et al. Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis 39, 186\u2013193 (2004).","journal-title":"Genesis"},{"key":"47124_CR37","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1002\/dvdy.20643","volume":"235","author":"JA Alva","year":"2006","unstructured":"Alva, J. A. et al. VE-Cadherin-Cre-recombinase transgenic mouse: a tool for lineage analysis and gene deletion in endothelial cells. Dev. Dyn. 235, 759\u2013767 (2006).","journal-title":"Dev. Dyn."},{"key":"47124_CR38","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1101\/gad.14.8.994","volume":"14","author":"S Marino","year":"2000","unstructured":"Marino, S., Vooijs, M., van Der Gulden, H., Jonkers, J. & Berns, A. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev. 14, 994\u20131004 (2000).","journal-title":"Genes Dev."},{"key":"47124_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0960-9822(00)00002-6","volume":"4","author":"T Jacks","year":"1994","unstructured":"Jacks, T. et al. Tumor spectrum analysis in p53-mutant mice. Curr. Biol. 4, 1\u20137 (1994).","journal-title":"Curr. Biol."},{"key":"47124_CR40","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nature02033","volume":"425","author":"S Gong","year":"2003","unstructured":"Gong, S. et al. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425, 917\u2013925 (2003).","journal-title":"Nature"},{"key":"47124_CR41","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":"47124_CR42","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nn.2467","volume":"13","author":"L Madisen","year":"2010","unstructured":"Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci 13, 133\u2013140 (2010).","journal-title":"Nat. Neurosci"},{"key":"47124_CR43","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-villus structures in vitro without a mesenchymal niche. Nature 459, 262\u2013265 (2009).","journal-title":"Nature"},{"key":"47124_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-021-04344-9","volume":"22","author":"DR Stirling","year":"2021","unstructured":"Stirling, D. R. et al. CellProfiler 4: improvements in speed, utility and usability. BMC Bioinformatics 22, 433 (2021).","journal-title":"BMC Bioinformatics"},{"key":"47124_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5","volume":"7","author":"P Bankhead","year":"2017","unstructured":"Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017).","journal-title":"Sci. Rep."},{"key":"47124_CR46","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.celrep.2013.09.005","volume":"5","author":"RC Mustata","year":"2013","unstructured":"Mustata, R. C. et al. Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium. Cell Rep. 5, 421\u2013432 (2013).","journal-title":"Cell Rep."},{"key":"47124_CR47","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":"47124_CR48","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"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-47124-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-47124-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-47124-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T06:05:10Z","timestamp":1713765910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-47124-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,8]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["47124"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-47124-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.04.27.538576","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,8]]},"assertion":[{"value":"3 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The HTML version of this article contained capitalization errors in figure 3, panels a, b, c and figure 4, panel a, b, in which \u2018P53\u2019 was used instead of \u2018p53\u2019. In addition, in figure 3, panels c, f, \u2018Dapi\u2019 was used instead of \u2018DAPI\u2019. The original HTML article of the article has been corrected. The PDF version was unaffected by this error.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"D.G.K. is a co-founder of and stockholder in XRad Therapeutics, which is developing radiosensitizers. D.G.K. is a member of the scientific advisory board and owns stock in Lumicell Inc., a company commercializing intraoperative imaging technology. None of these affiliations represents a conflict of interest with respect to the work described in this manuscript. D.G.K. is a coinventor on a patent for a handheld imaging device and is a coinventor on a patent for radiosensitizers. XRad Therapeutics, Merck, Bristol Myers Squibb, and Varian Medical Systems provided research support to D.G.K., but this did not support the research described in this manuscript. C.-L.L. reports research support from Rythera Therapeutics; however, this does not present a conflict of interest with the content of this manuscript. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3018"}}