Single-cell transcriptomic dissection of the cellular and molecular events underlying the triclosan-induced liver fibrosis in mice

作     者：Yun-Meng Bai Fan Yang Piao Luo Lu-Lin Xie Jun-Hui Chen Yu-Dong Guan Hong-Chao Zhou Teng-Fei Xu Hui-Wen Hao Bing Chen Jia-Hui Zhao Cai-Ling Liang Ling-Yun Dai Qing-Shan Geng Ji-Gang Wang Yun-Meng Bai;Fan Yang;Piao Luo;Lu-Lin Xie;Jun-Hui Chen;Yu-Dong Guan;Hong-Chao Zhou;Teng-Fei Xu;Hui-Wen Hao;Bing Chen;Jia-Hui Zhao;Cai-Ling Liang;Ling-Yun Da;Qing-Shan Geng;Ji-Gang Wang

作者机构：Department of NephrologyShenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People’s Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of UrologyShenzhen People’s Hospitalthe First Affiliated HospitalSouthern University Science and Technologythe Second Clinical Medical CollegeJinan UniversityShenzhen 518020China Integrated Chinese and Western Medicine Postdoctoral Research StationJinan UniversityGuangzhou 510632China Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center for Reproductive MedicineDongguan Maternal and Child Health Care HospitalSouthern Medical UniversityDongguan 523125GuangdongChina 

出 版 物：《Military Medical Research》 (军事医学研究（英文版）)

年 卷 期：2023年第10卷第5期

页      面：599-619页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China(2020YFA0908000 and 2022YFC2303600) the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002) the National Natural Science Foundation of China(82141001,82274182,82173914,82074098,81903588 and 82003814) the Science and Technology Foundation of Shenzhen(JCYJ20210324115800001) the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases) the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZXKT18003) the Fundamental Research Funds for the Central public welfare research institutes(ZZ14-YQ-050) the National Key R&D Program of China Key projects for international cooperation on science,technology and innovation(2020YFE0205100) the Shenzhen Governmental Sustainable Development Fund(KCXFZ20201221173612034) the Shenzhen Governmental Sustainable Development Fund(KCXFZ20201221173612034) the Shenzhen key Laboratory of Kidney Diseases(ZDSYS201504301616234) the Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(SZGSP001) the Shenzhen Key Laboratory of Kidney Diseases(ZDSYS201504301616234) the Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(SZGSP001) partially supported by a Grant from the Sanming Project of Medicine in Shenzhen(SZSM201612034) 

主　　题：Triclosan Single cell RNA sequencing Liver fibrogenesis Hepatic stellate cell 

摘      要：Background: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation ***: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing(scRNA-seq) was then carried out on TCS-or mock-treated mice livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor(TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the cellular and molecular events after TCS exposure. To verify the TCS-induced liver fibrosis,the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red stainings. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic ***: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control groups profiled the gene expressions of 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells(HSCs)were significantly increased in TCS-