NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development

0576977 - BTÚ 2024 RIV US eng J - Journal Article
Bohuslavová, Romana - Fabriciová, Valeria - Smolík, Ondřej - Lebron-Mora, Laura - Abaffy, Pavel - Benešová, Šárka - Žucha, Daniel - Valihrach, Lukáš - Berková, Z. - Saudek, F. - Pavlínková, Gabriela
NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development.
Nature Communications. Roč. 14, č. 1 (2023), č. článku 5554. E-ISSN 2041-1723
R&D Projects: GA ČR(CZ) GA19-07378S; GA MŠMT(CZ) LM2018126; GA ČR(CZ) GA22-11516S; GA MŠMT(CZ) EF18_046/0016045; GA MŠMT EF18_046/0015861
Institutional support: RVO:86652036
Keywords : SLET BETA-CELL * TRANSCRIPTION FACTORS * GLUCOSE-METABOLISM
OECD category: Endocrinology and metabolism (including diabetes, hormones)
Impact factor: 16.6, year: 2022
Method of publishing: Open access
https://www.nature.com/articles/s41467-023-41306-6

NEUROD1 is a transcription factor that helps maintain a mature phenotype of pancreatic & beta, 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.
Permanent Link: https://hdl.handle.net/11104/0346793