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ISL1 controls pancreatic alpha cell fate and beta cell maturation
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SYSNO ASEP 0571545 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title ISL1 controls pancreatic alpha cell fate and beta cell maturation Author(s) Bohuslavová, Romana (BTO-N) RID
Fabríciová, Valeria (BTO-N)
Lebrón Mora, Laura (BTO-N)
Malfatti, Jessica (BTO-N)
Smolík, Ondřej (BTO-N)
Valihrach, Lukáš (BTO-N) RID, ORCID
Benešová, Šárka (BTO-N)
Žucha, Daniel (BTO-N) ORCID
Berková, Z. (CZ)
Saudek, F. (CZ)
Evans, S. M. (US)
Pavlínková, Gabriela (BTO-N) RID, ORCIDNumber of authors 12 Article number 53 Source Title Cell and Bioscience. - : BioMed Central - ISSN 2045-3701
Roč. 13, č. 1 (2023)Number of pages 24 s. Language eng - English Country GB - United Kingdom Keywords Pancreatic endocrine cells ; Epigenetic histone modification ; Transcriptome ; Pancreas development Subject RIV EB - Genetics ; Molecular Biology OECD category Developmental biology R&D Projects GA19-07378S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support BTO-N - RVO:86652036 UT WOS 000948348700001 EID SCOPUS 85149989362 DOI https://doi.org/10.1186/s13578-023-01003-9 Annotation 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2024 Electronic address https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-023-01003-9
Number of the records: 1