潘一帆;秦会;刘薇;

• 1:大连理工大学环境学院工业生态与环境工程重点实验室

摘要(Abstract)：

超过3 000种全氟多氟化合物(per-and polyfluoroalkyl substances, PFASs)已被投入全球市场,大量新型替代品的环境效应与健康风险仍然未知,为PFASs的监管带来了极大的挑战。为揭示PFASs及新型替代品干扰的生物学过程和敏感靶基因,将人骨髓间充质干细胞(human bone mesenchymal stem cells, hBMSCs)暴露于氯代多氟醚基磺酸(chlorinated polyfluoroalkyl ether sulfonates, Cl-PFESAs)、全氟辛烷磺酸(perfluorooctane sulfonate, PFOS)、全氟己烷磺酸(perfluorohexane sulfonate, PFHxS)和全氟辛酸(perfluorooctanoic acid, PFOA),利用加权基因共表达网络分析(weighted gene co-expression network analysis, WGCNA)方法比较细胞基因表达谱的变化。WGCNA使用拓扑重叠计算5 004个基因间的关联程度,并结合动态剪切树法将其划分为14个通过颜色区分的基因模块,除灰色模块外各模块内的基因高度相关。基因模块与细胞样本相关性分析发现,对照组细胞基因表达谱与Blue和Greenyellow模块正相关,PFOS暴露组与Blue模块显著负相关,Cl-PFESAs暴露组与Greenyellow模块显著负相关,表明PFASs暴露使细胞中Blue和Greenyellow模块基因表达模式发生较大变化。Blue和Greenyellow模块显著富集的生物学过程主要为胆固醇生物合成和骨髓白细胞分化负调控,提示免疫调控和脂质代谢可能是多种PFASs作用于hBMSCs的共同潜在靶点。根据模块基因共表达网络的连通性筛选枢纽基因,发现与脂质代谢相关的DHCR24、SQLE和EBP基因可能是PFASs影响脂质代谢的敏感作用靶基因。进一步利用hBMSCs体外模型研究PFASs的相关毒性作用和机制,有助于建立该类化学物毒性预测和筛选的生物标志物,为其安全性评价和监管提供科学依据和新方法。

关键词(KeyWords)： 全氟和多氟烷基化合物;间充质干细胞;加权基因共表达网络分析;免疫调控;脂质代谢

Abstract:

Keywords:

基金项目(Foundation): 国家重点研发计划项目(2016YFC0401108);; 国家自然科学基金项目(21777020)

作者(Author): 潘一帆;秦会;刘薇;

Email:

DOI:

参考文献(References)：

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