Disturbance in transcriptomic profile, proliferation and multipotency in human mesenchymal stem cells caused by hexafluoropropylene oxides

• Published in: Environmental pollution (1987) 2022-01, Vol.292 (Pt B), p.118483, Article 118483
• Main Authors: Pan, Yifan, Qin, Hui, Zheng, Lu, Guo, Yong, Liu, Wei
• Format: Article
• Language: English
• Subjects: Cell Proliferation; Fluorocarbons - toxicity; Hexafluoropropylene oxides; Human mesenchymal stem cells; Humans; Hydrocarbons, Fluorinated - toxicity; Mesenchymal Stem Cells; Multipotency; Osteogenesis; Proliferation; Propionates - toxicity; Transcriptome; Transcriptomics
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2021.118483

As alternatives to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA) have raised concerns of their potential health risks. Human bone marrow mesenchymal stem cell was employed as an in vitro model to investigate the molecular targets and the adverse effects of HFPOs in stem cells in concentrations range starting at human relevant levels. Unsupervised transcriptomic analysis identified 1794 and 1429 DEGs affected by HFPO-TA and HFPO-DA, respectively. Cell cycle-associated biological processes were commonly altered by both chemicals. 18 and 35 KEGG pathways were enriched in HFPO-TA and HFPO-DA treatment group, respectively, among which multiple pathways were related to cancer and pluripotency. Few genes in PPAR signalling pathway were disturbed by HFPOs suggesting the involvement of PPAR-independent toxic mechanism. HFPO-TA promoted cell proliferation with significance at 1 μM mRNA levels of CDK and MYC were down-regulated by HFPOs, suggesting the negative feedback regulation to the abnormal cell proliferation. Decreased expression of CD44 protein, and ENG and THY1 mRNA levels demonstrated HFPOs-caused changes of hBMSCs phenotype. The osteogenic differentiation was also inhibited by HFPOs with reduced formation of calcium deposition. Furthermore, gene and protein expression of core pluripotency regulators NANOG was enhanced by HFPO-TA. The present study provides human relevant mechanistic evidence for health risk assessment of HFPOs, prioritizing comprehensive carcinogenicity assessment of this type of PFOA alternatives. [Display omitted] •hBMSCs were exposed to HFPOs at concentrations ranging from human relevant levels.•Gene profiles enriched multiple cancer-related pathways and pluripotency pathway.•HFPO-TA promoted cell proliferation with significance at 1 μM.•CDK and MYC decreased and was indicative of negative feedback.•CD44 in undifferentiated cell and osteogenetic calcium deposition were decreased.