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Surface water extracts impair gene profiles and differentiation in human mesenchymal stem cells

Zhang, Zhou, Liu, Wei, Hu, Junxiang, Qu, Yuanyuan, Zhao, Jing, Pan, Yifan, Zhang, Xin, Quan, Xie
Environment international 2019
Danio rerio, adipogenesis, bone formation, cell viability, cluster analysis, dose response, genes, health effects assessments, human diseases, human health, humans, interleukin-6, interleukin-8, long term effects, mesenchymal stromal cells, models, pollutants, principal component analysis, rheumatoid arthritis, rivers, screening, surface water, transcriptomics
Low concentrations of pollutants in surface water challenge the assessment of chronic effects to human health. Human bone mesenchymal stem cells (hBMSCs) were employed as a sensitive and relevant in vitro model to evaluate the potential biological effects caused by mixtures of pollutants in surface water. Organic extracts of surface water collected from Hun River inhibited cell viability in a dose-dependent manner. Surface water extracts at noncytotoxic concentrations induced 673 to 1136 differentially expressed genes (DEGs) in hBMSCs after 48 h of exposure. Total of 453 genes were commonly affected by surface water from different sites and account for 39.9–67.1% of DEGs induced by individual sample. Pathway enrichment analysis resulted in the pathways related to human diseases, genetic information processing and organismal systems. Interleukins (IL1B, IL6 and IL8) were affected and involved in most human diseases related pathways. The significantly downregulation of COL1A1 and the variation of rheumatoid arthritis pathway suggested that surface water potentially inhibited osteogenic differentiation of hBMSCs. Clustering analysis and principle component analysis with DEGs distinguish the surface water from tributary and mainstream. The crossing-species comparison of transcriptomic changes identified 1003 and 2715 differentially expressed orthologs in hBMSCs and zebrafish, respectively. After the exposure was removed, the followed osteogenic and adipogenic differentiation in hBMSCs for 14 days were inhibited by treatment during undifferentiated period, whereas the non-polar fraction exhibited stronger potency in affecting differentiation than the mid and polar fractions. hBMSCs, combining unsupervised omic technique and specific endpoints test, in promising in screening the health effects of environmental mixtures in surface water.