Loss of the Transcription Factor MAFB Limits β-cell Derivation from Human PSCs

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jun 4

PMID 32488111

Citations 29

Authors

Ronan Russell

Phichitpol P Carnese

Thomas G Hennings

Emily M Walker

Holger A Russ

Jennifer S Liu

Simone Giacometti

Roland Stein

Matthias Hebrok

Affiliations

Soon will be listed here.

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.

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