Effect of HNF1A-MODY on stem cell islets [II]

This project investigates the impact of the hotspot mutation P291fsinsC in HNF1A-MODY (Maturity-Onset Diabetes of the Young) on stem cell-derived islets. RNA sequencing (RNA-seq) was performed on islets differentiated from mutant and control HNF1A-MODY stem cells to study the mutation's effect on gene expression. By comparing the transcriptomic profiles of these islets, the study aims to uncover molecular mechanisms underlying the dysfunction caused by the P291fsinsC mutation during islet development and maturation. Overall design: HNF1A-MODY stem cells with the P291fsinsC hotspot mutation and wild-type controls were differentiated into the posterior foregut. The Sonic Hedgehog (SHH) pathway was manipulated by removing SANT1 of the differenciation protocol at the start of the stage to assess its effect on the differentiation process and evaluate the impact of the mutation on this developmental stage. Samples where taken at different timpoint along the differentation.