HNF1α maintains pancreatic α and β cell functions in primary human islets.

ABSTRACT: HNF1A haploinsufficiency underlies the most common form of human monogenic diabetes (HNF1A-maturity onset diabetes of the young [HNF1A-MODY]), and hypomorphic HNF1A variants confer type 2 diabetes risk. But a lack of experimental systems for interrogating mature human islets has limited our understanding of how the transcription factor HNF1α regulates adult islet function. Here, we combined conditional genetic targeting in human islet cells, RNA-Seq, chromatin mapping with cleavage under targets and release using nuclease (CUT&RUN), and transplantation-based assays to determine HNF1α-regulated mechanisms in adult human pancreatic α and β cells. Short hairpin RNA-mediated (shRNA-mediated) suppression of HNF1A in primary human pseudoislets led to blunted insulin output and dysregulated gluca

SUBMITTER: Qian MF 

PROVIDER: S-EPMC10807710 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature