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

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