{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:39:44Z","timestamp":1787611184044,"version":"build-2736575974"},"reference-count":102,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T00:00:00Z","timestamp":1633737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["Grant-in-Aid for Scientific Research (C) JP17K07495 and  JP20K06751"],"award-info":[{"award-number":["Grant-in-Aid for Scientific Research (C) JP17K07495 and  JP20K06751"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intestinal epithelial cells (IECs) are crucial for the digestive process and nutrient absorption. The intestinal epithelium is composed of the different cell types of the small intestine (mainly, enterocytes, goblet cells, Paneth cells, enteroendocrine cells, and tuft cells). The small intestine is characterized by the presence of crypt-villus units that are in a state of homeostatic cell turnover. Organoid technology enables an efficient expansion of intestinal epithelial tissue in vitro. Thus, organoids hold great promise for use in medical research and in the development of new treatments. At present, the cholinergic system involved in IECs and intestinal stem cells (ISCs) are attracting a great deal of attention. Thus, understanding the biological processes triggered by epithelial cholinergic activation by acetylcholine (ACh), which is produced and released from neuronal and\/or non-neuronal tissue, is of key importance. Cholinergic signaling via ACh receptors plays a pivotal role in IEC growth and differentiation. Here, we discuss current views on neuronal innervation and non-neuronal control of the small intestinal crypts and their impact on ISC proliferation, differentiation, and maintenance. Since technology using intestinal organoid culture systems is advancing, we also outline an organoid-based organ replacement approach for intestinal diseases.<\/jats:p>","DOI":"10.3390\/ijms222010912","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:23:25Z","timestamp":1633901005000},"page":"10912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Modeling Intestinal Stem Cell Function with Organoids"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-0939","authenticated-orcid":false,"given":"Toshio","family":"Takahashi","sequence":"first","affiliation":[{"name":"Suntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto 619-0284, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Fujishima","sequence":"additional","affiliation":[{"name":"Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto 606-8302, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mineko","family":"Kengaku","sequence":"additional","affiliation":[{"name":"Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto 606-8302, Japan"},{"name":"Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrm3721","article-title":"Adult intestinal stem cells: Critical drivers of epithelial homeostasis and regeneration","volume":"15","author":"Barker","year":"2014","journal-title":"Nat. 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