Repression of Progenitor Programs Safeguards Pancreatic Endocrine Cell Identity

ABSTRACT: Pancreatic endocrine cells regulate glucose homeostasis and energy metabolism in response to nutrients. All pancreatic endocrine cells originate from a common progenitor population through multiple coordinated cell fate decisions. ISL1 is a key lineage-determining transcription factor, but its role in endocrine cell identity, differentiation, and maturation is insufficiently characterized. By integrating single-cell RNA profiling with H3K27ac and H3K27me3 histone modification analyses, we identified a reshaped transcriptome and epigenetic landscape in Isl1-deficient endocrine cells leading to altered α-cell identity, loss of δ- and γ-cell lineages, and incompletely differentiated, immature β cells. We show that ISL1 represses intermediate developmental programs during endocrine cell differentiation and facilitates chromatin transitions to drive terminal differentiation and maturation. These findings provide insights into how combinatorial transcription factor-epigenome interactions activate and repress transcriptional programs driving cell fate acquisition, differentiation, and maturation during endocrine pancreas development.

ORGANISM(S): Mus musculus

PROVIDER: GSE297181 | GEO | 2026/05/14

REPOSITORIES: GEO