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

Russell, Carnese, Hennings, Walker, Russ, Liu, Giacometti, Stein, Hebrok (2020) Loss of the transcription factor MAFB limits β-cell derivation from human PSCs Nat Commun (IF: 16.6) 11(1) 2742

Abstract

Next generation sequencing studies have highlighted discrepancies in β-cells which exist between mice and men. Numerous reports have identified MAF BZIP Transcription Factor B (MAFB) to be present in human β-cells postnatally, while its expression is restricted to embryonic and neo-natal β-cells in mice. Using CRISPR/Cas9-mediated gene editing, coupled with endocrine cell differentiation strategies, we dissect the contribution of MAFB to β-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.

Links

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265500
http://www.ncbi.nlm.nih.gov/pubmed/32488111
http://dx.doi.org/10.1038/s41467-020-16550-9

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