State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, No. 163 Xianlin Avenue, Nanjing 210023, P. R. China.
Environ Sci Technol. 2020 Aug 4;54(15):9537-9546. doi: 10.1021/acs.est.0c02428. Epub 2020 Jul 21.
The embryonic period is a sensitive window for bisphenol A (BPA) exposure. However, embryonic development is a highly dynamic process with changing cell populations. The heterogeneity effects of BPA on fish embryo cells during development remain unclear. We applied single-cell RNA sequencing to analyze the impact of BPA exposure on transcriptome heterogeneity of 64 683 cells from zebrafish embryos at 8, 12, and 30 h postfertilization (hpf). Thirty-eight cell populations were identified and gene expression profiles of 16 cell populations were significantly altered by BPA. At 8 hpf, BPA mainly influenced the outer layer cell populations of embryos, such as neural plate border and enveloping layer cells. At 12 and 30 hpf, nervous system formation and heart morphogenesis were disturbed. The altered differential processes of the neural plate border, neural crest, and neuronal cells were found to lead to increased neurogenesis in zebrafish larvae. In the forebrain, midbrain, neurons, and optic cells, pathways related to cell division and DNA replication and repair were altered. Moreover, BPA also changed transforming growth factor (TGF) β signaling and heart tube morphogenesis in heart cells, leading to a decreased heartbeat in zebrafish larvae. Our study provides a comprehensive understanding of BPA toxicity on fish embryonic development at a single-cell level.
胚胎期是双酚 A（BPA）暴露的敏感窗口。然而，胚胎发育是一个高度动态的过程，细胞群体不断变化。BPA 对发育中鱼类胚胎细胞的异质性影响尚不清楚。我们应用单细胞 RNA 测序分析了 BPA 暴露对受精后 8、12 和 30 小时（hpf）斑马鱼胚胎 64683 个细胞转录组异质性的影响。鉴定出 38 个细胞群，其中 16 个细胞群的基因表达谱受到 BPA 的显著改变。在 8 hpf 时，BPA 主要影响胚胎的外层细胞群，如神经板边界和包被层细胞。在 12 和 30 hpf 时，神经系统形成和心脏形态发生受到干扰。神经板边界、神经嵴和神经元细胞的改变差异过程导致斑马鱼幼虫中的神经发生增加。在前脑、中脑、神经元和视细胞中，与细胞分裂和 DNA 复制和修复相关的途径发生改变。此外，BPA 还改变了心脏细胞中的转化生长因子（TGF）β信号和心脏管形态发生，导致斑马鱼幼虫心跳减少。我们的研究在单细胞水平上全面了解了 BPA 对鱼类胚胎发育的毒性。
