ISL1 controls pancreatic alpha cell fate and beta cell maturation

0571545 - BTÚ 2024 RIV GB eng J - Journal Article
Bohuslavová, Romana - Fabriciová, Valeria - Lebron-Mora, Laura - Malfatti, Jessica - Smolík, Ondřej - Valihrach, Lukáš - Benešová, Šárka - Žucha, Daniel - Berková, Z. - Saudek, F. - Evans, S. M. - Pavlínková, Gabriela
ISL1 controls pancreatic alpha cell fate and beta cell maturation.
Cell and Bioscience. Roč. 13, č. 1 (2023), č. článku 53. E-ISSN 2045-3701
R&D Projects: GA ČR(CZ) GA19-07378S
Institutional support: RVO:86652036
Keywords : Pancreatic endocrine cells * Epigenetic histone modification * Transcriptome * Pancreas development
OECD category: Biochemistry and molecular biology
Impact factor: 7.5, year: 2022
Method of publishing: Open access
https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-023-01003-9

BackgroundGlucose homeostasis is dependent on functional pancreatic alpha and ss cells. The mechanisms underlying the generation and maturation of these endocrine cells remain unclear.ResultsWe unravel the molecular mode of action of ISL1 in controlling alpha cell fate and the formation of functional ss cells in the pancreas. By combining transgenic mouse models, transcriptomic and epigenomic profiling, we uncover that elimination of Isl1 results in a diabetic phenotype with a complete loss of alpha cells, disrupted pancreatic islet architecture, downregulation of key ss-cell regulators and maturation markers of ss cells, and an enrichment in an intermediate endocrine progenitor transcriptomic profile.ConclusionsMechanistically, apart from the altered transcriptome of pancreatic endocrine cells, Isl1 elimination results in altered silencing H3K27me3 histone modifications in the promoter regions of genes that are essential for endocrine cell differentiation. Our results thus show that ISL1 transcriptionally and epigenetically controls alpha cell fate competence, and ss cell maturation, suggesting that ISL1 is a critical component for generating functional alpha and ss cells.
Permanent Link: https://hdl.handle.net/11104/0342714