{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:06:43Z","timestamp":1779286003597,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,18]]},"group-title":"Cell Biology","reference-count":52,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["R01DK128346"],"award-info":[{"award-number":["R01DK128346"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["R03DK121061"],"award-info":[{"award-number":["R03DK121061"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["P30DK098722"],"award-info":[{"award-number":["P30DK098722"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["T32DK007762"],"award-info":[{"award-number":["T32DK007762"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008069","name":"University of California, San Francisco","doi-asserted-by":"crossref","award":["Chancelor\u2019s Fund"],"award-info":[{"award-number":["Chancelor\u2019s Fund"]}],"id":[{"id":"10.13039\/100008069","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008069","name":"University of California, San Francisco","doi-asserted-by":"crossref","award":["Chan Future of UCSF"],"award-info":[{"award-number":["Chan Future of UCSF"]}],"id":[{"id":"10.13039\/100008069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,17]]},"abstract":"<jats:p>\n                  Stem cell renewal and crypt survival are tightly controlled processes critical for gut repair. Defining key regulators of intestinal healing is critical for the development of new epithelial-targeted therapies. We previously showed that the nuclear receptor LRH-1 (NR5A2) maintains intestinal epithelial health and protects against inflammatory damage. Here, using lineage tracing and selective LRH-1 knockout in the Atoh1\n                  <jats:sup>+<\/jats:sup>\n                  secretory lineage we show LRH-1 is vital for intestinal stem cell (ISC) regeneration in complementary in vivo and ex vivo injury-recovery models. Transcriptomic profiling and pathway analysis reveal downregulation of ER stress and unfolded protein response (UPR) programs. Using a new in vivo model to ascertain how LRH-1 directly impacts intestinal cell responses, we identify key ER stress response genes Ire1\u03b1 and Xbp1 as potential LRH-1 targets. Together our results uncover a novel mechanism whereby LRH-1 sustains the IRE1\u03b1-XBP1 arm of the UPR to support injury-induced dedifferentiation and ISC regeneration. Our findings highlight LRH-1 as a promising therapeutic target for restoring epithelial integrity in inflammatory intestinal disorders.\n                <\/jats:p>","DOI":"10.64898\/2026.05.15.725547","type":"posted-content","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T08:25:14Z","timestamp":1779092714000},"source":"Crossref","is-referenced-by-count":0,"title":["Nuclear Receptor Liver Receptor Homolog-1 drives Intestinal Stem Cell regeneration and UPR\/ER stress response after gut injury"],"prefix":"10.64898","author":[{"given":"Hsi-Ju","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, University of California San Francisco USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina N","family":"Braverman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, University of California San Francisco USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bohan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, University of California San Francisco USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R","family":"Bayrer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, University of California San Francisco 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