한빛사논문
- 조회1,741
Ting Zhou1, Tae Wan Kim2,3, Chi Nok Chong1, Lei Tan1,4, Sadaf Amin1, Zohreh Sadat Badieyan1, Suranjit Mukherjee1, Zaniar Ghazizadeh1, Hui Zeng1, Min Guo1, Miguel Crespo1, Tuo Zhang5, Reyn Kenyon1, Christopher L. Robinson1, Effie Apostolou6, Hui Wang4, Jenny Zhaoying Xiang5, Todd Evans1, Lorenz Studer2,3,* & Shuibing Chen1,7,*
1Department of Surgery, Weill Cornell Medical College, 1300 York Ave, New York 10065 NY, USA. 2The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY 10065, USA. 3 Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, NY 10065, USA. 4 School of Public health, Shanghai Jiao Tong University, School of Medicine, Shanghai 200000, China. 5 Genomic Resource Core Facility, Weill Cornell Medical College, 1300 York Ave, New York 10065 NY, USA. 6Department of Medicine, Weill Cornell Medical College, 1300 York Ave, New York 10065 NY, USA. 7Department of Biochemistry, Weill Cornell Medical College, 1300 York Ave, New York 10065 NY, USA.
These authors contributed equally: Ting Zhou, Tae Wan Kim
*Correspondence to Lorenz Studer or Shuibing Chen
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.
논문정보
- Research article
- 2018년 11월 (BRIC 등록일 2018-11-22)
- 국외 연구진
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