A hPSC-based platform to discover gene-environment interactions that impact human β-cell and dopamine neuron survival.

ABSTRACT: Common disorders, including diabetes and Parkinson's disease, are caused by a combination of environmental factors and genetic susceptibility. However, defining the mechanisms underlying gene-environment interactions has been challenging due to the lack of a suitable experimental platform. Using pancreatic β-like cells derived from human pluripotent stem cells (hPSCs), we discovered that a commonly used pesticide, propargite, induces pancreatic β-cell death, a pathological hallmark of diabetes. Screening a panel of diverse hPSC-derived cell types we extended this observation to a similar susceptibility in midbrain dopamine neurons, a cell type affected in Parkinson's disease. We assessed gene-environment interactions using isogenic hPSC lines for genetic variants associated with diabetes a

SUBMITTER: Zhou T 

PROVIDER: S-EPMC6240096 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature