Work on genetic variants in ONECUT1 associated to diabetes accepted in Nature Medicine

In a joint effort, the Institute for Computational Genomics at the Uniklinik RWTH Aachen and collaborators from Ulm University (Germany) and the Cochin Institute (Paris, France) have characterized the role of the transcription factor ONECUT1 in diabetes, which was recently published in Nature Medicine. The study includes a detailed clinical and genetic characterization of a consanguineous family, which shown that complete ONECUT1 deficiency results in neonatal diabetes and partial ONECUT1 deficiency leads to adult-onset diabetes. Next, the team used directed differentiation of pluripotent stem cells to study the functional consequences of ONECUT1 mutations. Computational analysis of sequencing from pancreatic progenitors performed by the team of Prof. Costa indicated the impairment of pancreas differentiation upon ONECUT1 mutation. Moreover, his team characterized regulatory regions near important pancreas genes NKX6-1 and NKX2-2, which are controlled by ONECUT1 and become inactive with ONECUT1 mutations leading to differentiation defects.