Dissection of molecular mechanisms of liver injury induced by microcystin-leucine arginine via single-cell RNA-sequencing  

作　　者：Yunmeng Bai Yali Song Miaoran Li Jinhuan Ou Hong Hu Nan Xu Min Cao SiyuWang Lin Chen Guangqing Cheng Zhijie Li Gang Liu Jigang Wang Wei Zhang Chuanbin Yang 

机构地区：[1]Dongguan Maternal and Child Health Care Hospital,Postdoctoral Innovation Practice Base of Southern Medical University,Dongguan 523125,China [2]Department of Rehabilitation Medicine,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China [3]Division of Thyroid and Breast Surgery,Shenzhen People’s Hospital(The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen 518020,China [4]Faculty of Brain Sciences,University College London,WC1E 6BT,UK [5]State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs,Artemisinin Research Center,and Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

出　　处：《Journal of Environmental Sciences》2024年第11期164-179,共16页环境科学学报（英文版）

基　　金：supported by the National Key Research and Development Program of China(Nos.2020YFA0908000 and 2022YFC2303600);the Guangdong-Dongguan Joint Fund Regional Cultivation Project(No.2021B1515140033);the Dongguan Science and Technology of Social Development Program(No.20221800905732);the National Natural Science Foundation of China(Nos.82074098,82374063,82274182,81841001,and 82173914);the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases),Shenzhen Science and Technology Innovation Commission(Nos.JCYJ20220818102613029,JCYJ20210324114014039,and JCYJ20210324115800001);Guangdong Basic and Applied Basic Research Foundation(No.2020A1515110549);the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202002);Shenzhen Governmental Sustainable Development Fund(No.KCXFZ20201221173612034);Shenzhen key Laboratory of Kidney Diseases(No.ZDSYS201504301616234);Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(No.SZGSP001).

摘　　要：The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern.Microcystin-leucine arginine(MC-LR)is a well-established toxin produced by cyanobacterial blooms,which is widely distributed in eutrophic waters.MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals.However,the underlying mechanisms of MCLR-induced liver toxicity are unclear.Herein,we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice.We established the first single-cell atlas ofmouse livers in response to MC-LR.Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treatedwith MC-LR are highly heterogeneous.Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3,which potentially contributed to hepatocyte apoptosis in response to MC-LR.Moreover,MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes.Furthermore,the MC-LR increased several subtypes of CD8+T cells with highly expressed multiple cytokines and chemokines.Overall,apart from directly inducing hepatocytes apoptosis,MC-LR activated proinflammatory Kupffer cell and CD8+T cells,and their interaction may constitute a hostile microenvironment that contributes to liver injury.Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.

关 键 词：MC-LR Liver toxicity Single-cell RNA sequencing Immune response Inflammatory responses 

分 类 号：X52[环境科学与工程—环境工程]