Murine Perinatal β-Cell Proliferation and the Differentiation of Human Stem Cell-Derived Insulin-Expressing Cells Require NEUROD1.

Abstract:

:Inactivation of the β-cell transcription factor NEUROD1 causes diabetes in mice and humans. In this study, we uncovered novel functions of NEUROD1 during murine islet cell development and during the differentiation of human embryonic stem cells (HESCs) into insulin-producing cells. In mice, we determined that Neurod1 is required for perinatal proliferation of α- and β-cells. Surprisingly, apoptosis only makes a minor contribution to β-cell loss when Neurod1 is deleted. Inactivation of NEUROD1 in HESCs severely impaired their differentiation from pancreatic progenitors into insulin-expressing (HESC-β) cells; however, survival or proliferation was not affected at the time points analyzed. NEUROD1 was also required in HESC-β cells for the full activation of an essential β-cell transcription factor network. These data reveal conserved and distinct functions of NEUROD1 during mouse and human β-cell development and maturation, with important implications about the function of NEUROD1 in diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Romer AI,Singer RA,Sui L,Egli D,Sussel L

doi

10.2337/db19-0117

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

2259-2271

issue

12

eissn

0012-1797

issn

1939-327X

pii

db19-0117

journal_volume

68

pub_type

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