YAP inhibition enhances the differentiation of functional stem cell-derived insulin-producing β cells.

ABSTRACT: Stem cell-derived insulin-producing beta cells (SC-β) offer an inexhaustible supply of functional β cells for cell replacement therapies and disease modeling for diabetes. While successful directed differentiation protocols for this cell type have been described, the mechanisms controlling its differentiation and function are not fully understood. Here we report that the Hippo pathway controls the proliferation and specification of pancreatic progenitors into the endocrine lineage. Downregulation of YAP, an effector of the pathway, enhances endocrine progenitor differentiation and the generation of SC-β cells with improved insulin secretion. A chemical inhibitor of YAP acts as an inducer of endocrine differentiation and reduces the presence of proliferative progenitor cells. Conversely, su

SUBMITTER: Rosado-Olivieri EA 

PROVIDER: S-EPMC6443737 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature