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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