Transient FOXO1 inhibition in pancreatic endoderm promotes the generation of NGN3+ endocrine precursors from human iPSCs.
FOXO1
Induced pluripotent stem cell
NGN3
Pancreatic endocrine cells
Wnt
Journal
Stem cell research
ISSN: 1876-7753
Titre abrégé: Stem Cell Res
Pays: England
ID NLM: 101316957
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
07
08
2019
revised:
24
01
2020
accepted:
27
02
2020
pubmed:
18
3
2020
medline:
22
6
2021
entrez:
18
3
2020
Statut:
ppublish
Résumé
In the multi-step differentiation protocol used to generate pancreatic endocrine cells from human pluripotent stem cells, the induction of NGN3+ endocrine precursors from the PDX1+/NKX6.1+ pancreatic endoderm is crucial for efficient endocrine cell production. Here, we demonstrate that transient, not prolonged FOXO1 inhibition results in enhanced NGN3+ endocrine precursors and hormone-producing cell production. FOXO1 inhibition does not directly induce NGN3 expression but stimulates PDX1+/NKX6.1+ cell proliferation. NOTCH activity, whose suppression is important for Ngn3 expression, is not suppressed but Wnt signaling is stimulated by FOXO1 inhibition. Reversely, Wnt inhibition suppresses the effects of FOXO1 inhibitor. These findings indicate that FOXO1 and Wnt are involved in regulating the proliferation of PDX1+/NKX6.1+ pancreatic endoderm that gives rise to NGN3+ endocrine precursors.
Identifiants
pubmed: 32179491
pii: S1873-5061(20)30058-1
doi: 10.1016/j.scr.2020.101754
pii:
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
FOXO1 protein, human
0
Forkhead Box Protein O1
0
Homeodomain Proteins
0
Trans-Activators
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101754Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.