{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:21:25Z","timestamp":1790454085545,"version":"4.1.0"},"posted":{"date-parts":[[2026,7,30]]},"group-title":"Molecular Biology","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R01DK117005"],"award-info":[{"award-number":["R01DK117005"]}]},{"name":"NIH","award":["R01GM156796"],"award-info":[{"award-number":["R01GM156796"]}]},{"name":"NIH","award":["S10OD030402"],"award-info":[{"award-number":["S10OD030402"]}]},{"name":"Hungarian National Research","award":["TKP2021-EGA-42"],"award-info":[{"award-number":["TKP2021-EGA-42"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["19K08454"],"award-info":[{"award-number":["19K08454"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["22K06071"],"award-info":[{"award-number":["22K06071"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,30]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  The circadian clock regulates diverse cellular processes, including intestinal epithelial cell (IEC) proliferation. However, mechanisms regulating clock-dependent IEC differentiation remain unknown. We performed a time course RNA-Seq using the mouse small intestine and identified NOTCH signaling, a key mechanism regulating IEC differentiation, as one of the pathways under the control of circadian rhythms. Using mouse enteroids, we discovered that a NOTCH reporter, Hes1-luciferase, exhibits both ultradian or circadian oscillations depending on the stemness of mouse enteroids. Furthermore, single-cell analysis of Hes1-mCherry revealed that the period of\n                  <jats:italic>Hes1<\/jats:italic>\n                  oscillations varies widely, but circadian rhythms modulate the number of Hes1-mCherry+ cells in the population. Finally, we show that Paneth cell numbers fluctuate over the circadian cycle, suggesting that circadian clock-regulated\n                  <jats:italic>Hes1<\/jats:italic>\n                  drives the circadian dynamics of IEC composition. Our study provides a deeper insight into circadian regulation of IEC differentiation, which will be critical for applications of chronotherapies for digestive diseases.\n                <\/jats:p>","DOI":"10.64898\/2026.07.30.741736","type":"posted-content","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:50:21Z","timestamp":1785451821000},"source":"Crossref","is-referenced-by-count":1,"title":["Circadian clock regulates intestinal epithelial cell differentiation via NOTCH\/Hes1 oscillations"],"prefix":"10.64898","author":[{"given":"Sevde","family":"Goker","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neurobiology, University of Cincinnati, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suengwon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neurobiology, University of Cincinnati, Cincinnati, OH 45267, 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