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
Diabetesjournal_title
Diabetesauthors
Romer AI,Singer RA,Sui L,Egli D,Sussel Ldoi
10.2337/db19-0117subject
Has Abstractpub_date
2019-12-01 00:00:00pages
2259-2271issue
12eissn
0012-1797issn
1939-327Xpii
db19-0117journal_volume
68pub_type
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