Maturity-onset diabetes of the young (MODY) is a type of autosomal dominant monogenic diabetes classically characterized by non-ketotic, non-insulin-dependent diabetes occurring before the age of 25 years. Patients with MODY5 commonly exhibit pancreatic hypoplasia due to an autosomal dominant mutation in the HNF1B gene.
Previously, our collaborators from Joslin Diabetes Center, the research group of Rohit Kulkarni, turned skin cells (fibroblasts), donated by Norwegian patients, into induced pluripotent stem (iPS) cells, which are cells that can be coaxed to develop any tissue in the body. Now, using a customised protocol, they differentiated these iPSC into pancreatic progenitors and compared family controls with 2 mutation carriers (of which one of them has developed diabetes, whereas the other has not). Time-course analyses revealed complex compensatory mechanisms acting at the transcriptional level. These data suggest that, even though the diabetes onset occurs relatively late in life, there are compensated perturbations early during pancreatic development. Future studies are required on later differentiation stages up to mature insulin-producing β-like cells, which should reveal the impact of transcriptional perturbations on β-cell formation and function.
The paper can be read here.
Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia Teo AK, Lau HH, Valdez IA, Dirice E, Tjora E, Raeder H, Kulkarni RN.
Stem Cell Reports. 2016 Feb 8. pii: S2213-6711(16)00024-2.