{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:44:36Z","timestamp":1787013876208,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008454","name":"Boehringer Ingelheim Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008454","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The mammalian gut is the largest endocrine organ. Dozens of hormones secreted by enteroendocrine cells regulate a variety of physiological functions of the gut but also of the pancreas and brain. Here, we examined the role of the helix\u2010loop\u2010helix transcription factor ID2 during the differentiation of intestinal stem cells along the enteroendocrine lineage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To assess the functions of ID2 in the adult mouse small intestine, we used single\u2010cell RNA sequencing, genetically modified mice, and organoid assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that in the adult intestinal epithelium\n                      <jats:italic>Id2<\/jats:italic>\n                      is predominantly expressed in enterochromaffin and peptidergic enteroendocrine cells. Consistently, the loss of\n                      <jats:italic>Id2<\/jats:italic>\n                      leads to the reduction of Chromogranin A\u2010positive enteroendocrine cells. In contrast, the numbers of tuft cells are increased in\n                      <jats:italic>Id2<\/jats:italic>\n                      mutant small intestine. Moreover, ablation of\n                      <jats:italic>Id2<\/jats:italic>\n                      elevates the numbers of Serotonin\n                      <jats:sup>+<\/jats:sup>\n                      enterochromaffin cells and Ghrelin\n                      <jats:sup>+<\/jats:sup>\n                      X\u2010cells in the posterior part of the small intestine. Finally, ID2 acts downstream of BMP signalling during the differentiation of Glucagon\u2010like peptide\u20101\n                      <jats:sup>+<\/jats:sup>\n                      L\u2010cells and Cholecystokinin\n                      <jats:sup>+<\/jats:sup>\n                      I\u2010cells towards Neurotensin\n                      <jats:sup>+<\/jats:sup>\n                      PYY\n                      <jats:sup>+<\/jats:sup>\n                      N\u2010cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ID2 plays an important role in cell fate decisions in the adult small intestine. First, ID2 is essential for establishing a differentiation gradient for enterochromaffin and X\u2010cells along the anterior\u2010posterior axis of the gut. Next, ID2 is necessary for the differentiation of N\u2010cells thus ensuring a differentiation gradient along the crypt\u2010villi axis. Finally, ID2 suppresses the commitment of secretory intestinal epithelial progenitors towards tuft cell lineage and thus controls host immune response to commensal and parasitic microbiota.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.13773","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T08:06:26Z","timestamp":1641369986000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["ID2 controls differentiation of enteroendocrine cells in mouse small intestine"],"prefix":"10.1111","volume":"234","author":[{"given":"Valeriya V.","family":"Zinina","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg\u2010University Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ruehle","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology 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