RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function.

ABSTRACT:

Aims/hypothesis

Regulatory factor X 6 (RFX6) is crucial for pancreatic endocrine development and differentiation. The RFX6 variant p.His293LeufsTer7 is significantly enriched in the Finnish population, with almost 1:250 individuals as a carrier. Importantly, the FinnGen study indicates a high predisposition for heterozygous carriers to develop type 2 and gestational diabetes. However, the precise mechanism of this predisposition remains unknown.

Methods

To understand the role of this variant in beta cell development and function, we used CRISPR technology to generate allelic series of pluripotent stem cells. We created two isogenic stem cell models: a human embryonic stem cell model; and a patient-derived stem cell model. Both were differentiated into pancreatic islet lineag

SUBMITTER: Ibrahim H 

PROVIDER: S-EPMC11343796 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature