pr7b00693_si_004.xlsx (471.53 kB)
Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells
dataset
posted on 2017-12-20, 21:14 authored by Yan Han, Jinghua Zhao, Ruili Huang, Menghang Xia, Daojing WangThe new strategy for chemical toxicity
testing and modeling is
to use in vitro human cell-based assays in conjunction with quantitative
high-throughput screening (qHTS) technology, to identify molecular
mechanisms and predict in vivo responses. Stem cells are more physiologically
relevant than immortalized cell lines because of their unique proliferation
and differentiation potentials. We established a robust two stem cells-two
lineages assay system, encompassing human mesenchymal stem cells (hMSCs)
along osteogenesis and human induced pluripotent stem cells (hiPSCs)
along hepatogenesis. We performed qHTS phenotypic screening of LOPAC1280
and identified 38 preliminary hits for hMSCs. This was followed by
validation of a selected number of hits and determination of their
IC50 values and mechanistic studies of idarubicin and cantharidin
treatments using proteomics and bioinformatics. In general, hiPSCs
were more sensitive than hMSCs to chemicals, and differentiated progenies
were less sensitive than their progenitors. We showed that chemical
toxicity depends on both stem cell types and their differentiation
stages. Proteomics identified and quantified over 3000 proteins for
both stem cells. Bioinformatics identified apoptosis and G2/M as the
top pathways conferring idarubicin toxicity. Our Omics-based assays
of stem cells provide mechanistic insights into chemical toxicity
and may help prioritize chemicals for in-depth toxicological evaluations.