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Robust differentiation of human enteroendocrine cells from intestinal stem cells.

Authors :
Zeve D
Stas E
de Sousa Casal J
Mannam P
Qi W
Yin X
Dubois S
Shah MS
Syverson EP
Hafner S
Karp JM
Carlone DL
Ordovas-Montanes J
Breault DT
Source :
Nature communications [Nat Commun] 2022 Jan 11; Vol. 13 (1), pp. 261. Date of Electronic Publication: 2022 Jan 11.
Publication Year :
2022

Abstract

Enteroendocrine (EE) cells are the most abundant hormone-producing cells in humans and are critical regulators of energy homeostasis and gastrointestinal function. Challenges in converting human intestinal stem cells (ISCs) into functional EE cells, ex vivo, have limited progress in elucidating their role in disease pathogenesis and in harnessing their therapeutic potential. To address this, we employed small molecule targeting of the endocannabinoid receptor signaling pathway, JNK, and FOXO1, known to mediate endodermal development and/or hormone production, together with directed differentiation of human ISCs from the duodenum and rectum. We observed marked induction of EE cell differentiation and gut-derived expression and secretion of SST, 5HT, GIP, CCK, GLP-1 and PYY upon treatment with various combinations of three small molecules: rimonabant, SP600125 and AS1842856. Robust differentiation strategies capable of driving human EE cell differentiation is a critical step towards understanding these essential cells and the development of cell-based therapeutics.<br /> (© 2022. The Author(s).)

Details

Language :
English
ISSN :
2041-1723
Volume :
13
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
35017529
Full Text :
https://doi.org/10.1038/s41467-021-27901-5