NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development

NEUROD1 is a transcription factor that helps maintain a mature phenotype of pancreatic β cells. Disruption of Neurod1 during 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 cru...

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Published in:Nature communications 2023-09, Vol.14 (1), p.5554-5554, Article 5554
Main Authors: Bohuslavova, Romana, Fabriciova, Valeria, Smolik, Ondrej, Lebrón-Mora, Laura, Abaffy, Pavel, Benesova, Sarka, Zucha, Daniel, Valihrach, Lukas, Berkova, Zuzana, Saudek, Frantisek, Pavlinkova, Gabriela
Format: Article
Language:English
Subjects:
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Beta cells
Beta2 protein
Cell differentiation
Cell fate
Chromatin
Diabetes
Diabetes mellitus
Differentiation
Genes
Histones
Humanities and Social Sciences
Inactivation
multidisciplinary
Neonates
Pancreas
Phenotypes
Science
Science (multidisciplinary)
Transcription factors
Transcriptomes
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Summary:NEUROD1 is a transcription factor that helps maintain a mature phenotype of pancreatic β cells. Disruption of Neurod1 during 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 that Neurod1 inactivation triggers a downregulation of endocrine differentiation transcription factors and upregulation of non-endocrine genes within the Neurod1 -deficient endocrine cell population, disturbing endocrine identity acquisition. Neurod1 deficiency 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. Errors during pancreas development and specification of the endocrine lineage can result in severe neonatal diabetes. Here they show that loss of NEUROD1 leads to disturbances in endocrine cell identity acquisition during pancreas development, with cellular reprogramming occurring at the single-cell level within both α- and β-cell populations.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-41306-6