Generation of pancreatic progenitors from human pluripotent stem cells by small molecules.

ABSTRACT: Human pluripotent stem cell (hPSC)-derived pancreatic progenitors (PPs) provide promising cell therapies for type 1 diabetes. Current PP differentiation requires a high amount of Activin A during the definitive endoderm (DE) stage, making it economically difficult for commercial ventures. Here we identify a dose-dependent role for Wnt signaling in controlling DE differentiation without Activin A. While high-level Wnt activation induces mesodermal formation, low-level Wnt activation by a small-molecule inhibitor of glycogen synthase kinase 3 is sufficient for DE differentiation, yielding SOX17⁺FOXA2⁺ DE cells. BMP inhibition further enhances this DE differentiation, generating over 87% DE cells. These DE cells could be further differentiated into PPs and functional β c

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC8452541 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature