Propargite, an environmental chemical, interacts with GWAS identified diabetes genes to impact human pancreatic ß-cell death [propargite treatment]

This paper describes the first time a high-content environmental chemicals screen using pancreatic ß-like cells derived from human pluripotent stem cells (hPSCs), and discovered that a commonly used pesticide, propargite, induces pancreatic ß-cell DNA damage and necrosis. More interestingly, we found out the genetic background of ß-like cells affects their response to propargite-induced toxicity, based on isogenic hPSC platform, including for variants GWAS identified associated with T1D, since isogenic GSTT1-/- and PTPN2-/- pancreatic ß-like cells are hypersensitive to propargite-induced ß-cell death both in vitro and in vivo. In summary, our study identified an environmental chemical that contributes to the loss of ß-cells and provides an innovative platform for using hPSC-derived cells to explore gene-environment interactions that impact diabetes disease progression. Overall design: RNA-seq was used to compare the gene expression in DMSO, DMSO+GSH, Propargite and Propargite+GSH treated hESC derived INS-GFP+ cells.

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Zhou T, Kim TW, Chong CN, Tan L, Amin S, Sadat Badieyan Z, Mukherjee S, Ghazizadeh Z, Zeng H, Guo M, Crespo M, Zhang T, Kenyon R, Robinson CL, Apostolou E, Wang H, Xiang JZ, Evans T, Studer L, Chen S