| First Author | Bohuslavova R | Year | 2023 |
| Journal | Cell Biosci | Volume | 13 |
| Issue | 1 | Pages | 53 |
| PubMed ID | 36899442 | Mgi Jnum | J:333987 |
| Mgi Id | MGI:7444225 | Doi | 10.1186/s13578-023-01003-9 |
| Citation | Bohuslavova R, et al. (2023) ISL1 controls pancreatic alpha cell fate and beta cell maturation. Cell Biosci 13(1):53 |
| abstractText | BACKGROUND: Glucose homeostasis is dependent on functional pancreatic alpha and ss cells. The mechanisms underlying the generation and maturation of these endocrine cells remain unclear. RESULTS: We 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. CONCLUSIONS: Mechanistically, 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. |
