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

Ronan Russell, Phichitpol P. Carnese, Thomas G. Hennings, Emily M. Walker, Holger A. Russ, Jennifer S. Liu, Simone Giacometti, Roland Stein and Matthias Hebrok ()
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Ronan Russell: University of California San Francisco
Phichitpol P. Carnese: University of California San Francisco
Thomas G. Hennings: University of California San Francisco
Emily M. Walker: Vanderbilt University
Holger A. Russ: University of California San Francisco
Jennifer S. Liu: University of California San Francisco
Simone Giacometti: University of California San Francisco
Roland Stein: Vanderbilt University
Matthias Hebrok: University of California San Francisco

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16550-9

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DOI: 10.1038/s41467-020-16550-9

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