{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T07:56:47Z","timestamp":1775894207724,"version":"3.50.1"},"posted":{"date-parts":[[2025,2,8]]},"group-title":"Physiology","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,8]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Constipation causes significant morbidity in Cystic Fibrosis (CF) patients. Using CF patient (F508del) derived\n                  <jats:italic>ex vivo<\/jats:italic>\n                  ileal and distal colonic\/rectal enteroids as a model and the Forskolin Induced Swelling Assay (FIS), we compared CFTR mediated fluid secretion in human enterocytes across the crypt-villus axis.\n                  <jats:underline>CFTR expression and FIS decreased as enterocytes differentiated from crypt to become partially differentiated and then mature villus cells<\/jats:underline>\n                  . While there was no FIS response in undifferentiated (crypt enterocytes) F508del-CF enteroids, partially differentiated F508del-CF enteroids had a swelling response to forskolin (cAMP) and linaclotide (cGMP) which was \u223c48%, and \u223c67% of the response in healthy enteroids, respectively and was prevented by a CFTR inhibitor. Also, linaclotide and a general PDE inhibitor independently enhanced combined CFTR-modulator-induced FIS response from partially differentiated F508del-CF enteroids. These findings demonstrate that partially differentiated ileal and distal colonic F508del-CFTR enteroids can be stimulated to secrete fluid by cAMP and cGMP.\n                <\/jats:p>","DOI":"10.1101\/2025.02.03.636268","type":"posted-content","created":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T15:55:19Z","timestamp":1739030119000},"source":"Crossref","is-referenced-by-count":0,"title":["Partially differentiated enterocytes in ileal and distal-colonic human F508del-CF-enteroids secrete fluid in response to forskolin and linaclotide"],"prefix":"10.64898","author":[{"given":"Yan","family":"Rong","sequence":"first","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo R.","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, P. 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Box 2040, 3000CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruxian","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafiq","family":"Sarker","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Boffelli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cedars-Sinai Guerin Children\u2019s, Los Angeles, Ca, 94143"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel 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