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


Authors: Zhou, T.; Kim, T. W.; Chong, C. N.; Tan, L.; Amin, S.; Sadat Badieyan, Z.; Mukherjee, S.; Ghazizadeh, Z.; Zeng, H.; Guo, M.; Crespo, M.; Zhang, T.; Kenyon, R.; Robinson, C. L.; Apostolou, E.; Wang, H.; Xiang, J. Z.; Evans, T.; Studer, L.; Chen, S.
Article Title: 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 and Parkinson's disease. We found GSTT1-/- pancreatic β-like cells and dopamine neurons were both hypersensitive to propargite-induced cell death. Our study identifies an environmental chemical that contributes to human β-cell and dopamine neuron loss and validates a novel hPSC-based platform for determining gene-environment interactions.
Journal Title: Nature Communications
Volume: 9
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2018-11-16
Start Page: 4815
Language: English
DOI: 10.1038/s41467-018-07201-1
PUBMED: 30446643
PROVIDER: scopus
PMCID: PMC6240096
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
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MSK Authors
  1. Lorenz Studer
    153 Studer
  2. Taewan Kim
    1 Kim