Loss of the transcription factor MAFB limits ?-cell derivation from human PSCs.

ABSTRACT: Next generation sequencing studies have highlighted discrepancies in ?-cells which exist between mice and men. Numerous reports have identified MAF BZIP Transcription Factor B (MAFB) to be present in human ?-cells postnatally, while its expression is restricted to embryonic and neo-natal ?-cells in mice. Using CRISPR/Cas9-mediated gene editing, coupled with endocrine cell differentiation strategies, we dissect the contribution of MAFB to ?-cell development and function specifically in humans. Here we report that MAFB knockout hPSCs have normal pancreatic differentiation capacity up to the progenitor stage, but favor somatostatin- and pancreatic polypeptide-positive cells at the expense of insulin- and glucagon-producing cells during endocrine cell development. Our results describe a requirement for MAFB late in the human pancreatic developmental program and identify it as a distinguishing transcription factor within islet cell subtype specification. We propose that hPSCs represent a powerful tool to model human pancreatic endocrine development and associated disease pathophysiology.

SUBMITTER: Russell R 

PROVIDER: S-EPMC7265500 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature