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

Low concentrations of pollutants in surface water challenge the assessment of chronic effects on 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 533 to 1055 differentially expressed genes (DEGs) in hBMSCs after 48 h of exposure. Total of 370 genes were commonly affected by surface water from different sites and accounted for 35-69% of DEGs impaired by individual sample. Pathways related to human diseases, genetic information processing and organismal systems were enriched based on DEGs. 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 923 and 2715 differentially expressed orthologs in hBMSCs and zebrafish, respectively. After the exposure ceased, the followed osteogenic and adipogenic differentiation in hBMSCs for 14 days were inhibited by the treatment of surface water during undifferentiated period, whereas the non-polar fraction exhibited stronger potency in affecting differentiation than the mid to polar fractions. hBMSCs, combining unsupervised transcriptomic technique and specific endpoints test, are promising in screening the health effects of environmental mixtures in surface water.