Erschienen:
Springer Science and Business Media LLC, 2023
Erschienen in:
Nature Communications, 14 (2023) 1
Sprache:
Englisch
DOI:
10.1038/s41467-023-41306-6
ISSN:
2041-1723
Entstehung:
Anmerkungen:
Beschreibung:
AbstractNEUROD1 is a transcription factor that helps maintain a mature phenotype of pancreatic β cells. Disruption ofNeurod1during pancreatic development causes severe neonatal diabetes; however, the exact role of NEUROD1 in the differentiation programs of endocrine cells is unknown. Here, we report a crucial role of the NEUROD1 regulatory network in endocrine lineage commitment and differentiation. Mechanistically, transcriptome and chromatin landscape analyses demonstrate thatNeurod1inactivation triggers a downregulation of endocrine differentiation transcription factors and upregulation of non-endocrine genes within theNeurod1-deficient endocrine cell population, disturbing endocrine identity acquisition.Neurod1deficiency altered the H3K27me3 histone modification pattern in promoter regions of differentially expressed genes, which resulted in gene regulatory network changes in the differentiation pathway of endocrine cells, compromising endocrine cell potential, differentiation, and functional properties.