| A single-cell survey unveils cellular heterogeneity and sensitive responses in mouse cortices induced by oral exposure to triphenyl phosphate | |
Ji, Di; Yu, Yuejin; Zhu, Qicheng; Li, Xianjie; Zhong, Xiali; Zhang, Zhuyi; Ke, Weijian; Niu, Congying; Wang, Can; Wu, Jingwei; Chen, Da; Song, Maoyong ; Wei, Yanhong
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| 2022-09 | |
| Source Publication | ARCHIVES OF TOXICOLOGY
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| ISSN | 0340-5761 |
| Volume | 96Issue:9Pages:2545-2557 |
| Abstract | Triphenyl phosphate (TPhP) is a non-halogenated organophosphorus flame retardant, and there is a higher exposure risk in children. TPhP has been found to be neurotoxic upon developmental exposure, yet the specific mechanism remains unclear. To characterize the cellular responses underlying TPhP-induced developmental neurotoxicity, we administered TPhP (0.5, 5 or 50 mg/kg/day) to neonatal mice from postnatal day 10 (P10)-P70. A total of 17,229 cells and 26,338 genes were identified in cortical samples from control and low-dose (the internal doses of metabolite DPhP comparable to human exposure level) groups using single-cell RNA sequencing (scRNA-seq). TPhP exposure led to heterogeneous transcriptional alterations and intercellular crosstalk among neurons, neural stem/progenitor cells (NSPCs), endothelial cells, and immunocytes. Deprivation of NSPCs, loss of mature neurons, and concomitant neuroinflammation mediated by extrinsic and intrinsic immunocytes were found in TPhP-exposed cortices. In addition, we observed blood-brain barrier destruction prior to the anxiety/depression-like neurobehavioral changes. These results reveal the distinctive cellular processes in TPhP's neurodevelopmental toxicity and uncover that the impeded neurogenesis, disrupted vascular barrier, and concomitant neuroinflammation are the sensitive responses to TPhP exposure. Our study paves the way for the application of scRNA-seq in toxicity assessments for emerging neurotoxic pollutants. |
| Department | 环境化学与生态毒理学国家重点实验室 ; 环境化学与生态毒理学国家重点实验室 |
| Keyword | ORGANOPHOSPHORUS FLAME RETARDANTS PLASTICIZERS METABOLISM TOXICITY CHILDREN ESTERS DUST P53 |
| Document Type | 期刊论文 |
| Identifier | https://ir.rcees.ac.cn/handle/311016/47459 |
| Collection | 环境化学与生态毒理学国家重点实验室 |
| Corresponding Author | Wei, Yanhong |
| Affiliation | 1.Sun Yat Sen Univ, Sch Publ Hlth, Dept Toxicol, Guangdong Prov Key Lab Food Nutr & Hlth, 74 Zhongshan Rd 2, Guangzhou 510080, Peoples R China 2.Jinan Univ, Sch Environm, Guangzhou 510632, Peoples R China 3.Jinan Univ, Guangdong Key Lab Environm Pollut & Hlth, Guangzhou 510632, Peoples R China 4.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China |
| Recommended Citation GB/T 7714 | Ji, Di,Yu, Yuejin,Zhu, Qicheng,et al. A single-cell survey unveils cellular heterogeneity and sensitive responses in mouse cortices induced by oral exposure to triphenyl phosphate[J]. ARCHIVES OF TOXICOLOGY,2022,96(9):2545-2557. |
| APA | Ji, Di.,Yu, Yuejin.,Zhu, Qicheng.,Li, Xianjie.,Zhong, Xiali.,...&Wei, Yanhong.(2022).A single-cell survey unveils cellular heterogeneity and sensitive responses in mouse cortices induced by oral exposure to triphenyl phosphate.ARCHIVES OF TOXICOLOGY,96(9),2545-2557. |
| MLA | Ji, Di,et al."A single-cell survey unveils cellular heterogeneity and sensitive responses in mouse cortices induced by oral exposure to triphenyl phosphate".ARCHIVES OF TOXICOLOGY 96.9(2022):2545-2557. |
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