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Single-cell RNA sequencing reveals the heterogeneity and intercellular communication of hepatic stellate cells and macrophages during liver fibrosis

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收录情况： ◇ ESCI

作者：
Cheng Sheng[1,2] * ; Zou Yunhan[3] * ; Zhang Man[4] * ; Bai Shihao[4] ; Tao Kun[5] ; Wu Jiaoxiang[2] ; Shi Yi[6,7] ; Wu Yuelan[2] ; Lu Yinzhong[2,8] ; He Kunyan[4] ; Sun Peng[1] ; Su Xianbin[4,7,*3] ; Hou Shangwei[8,*2] ; Han Bo[1,2,*1] ;
机构： [1]Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2]Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [3]Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China [4]Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China [5]Department of Pathology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China [6]Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China [7]eHealth Program of Shanghai Anti-Doping Laboratory, Shanghai University of Sport, Shanghai, China [8]Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
出处：
DOI： 10.1002/mco2.378

关键词： hepatic stellate cell heterogeneity intercellular crosstalk liver fibrosis macrophage ScRNAseq

摘要：
Uncontrolled and excessive progression of liver fibrosis is thought to be the prevalent pathophysiological cause of liver cirrhosis and hepatocellular cancer, and there are currently no effective antifibrotic therapeutic options available. Intercellular communication and cellular heterogeneity in the liver are involved in the progression of liver fibrosis, but the exact nature of the cellular phenotypic changes and patterns of interregulatory remain unclear. Here, we performed single-cell RNA sequencing on nonparenchymal cells (NPCs) isolated from normal and fibrotic mouse livers. We identified eight main types of cells, including endothelial cells, hepatocytes, dendritic cells, B cells, natural killer/T (NK/T) cells, hepatic stellate cells (HSCs), cholangiocytes and macrophages, and revealed that macrophages and HSCs exhibit the most variance in transcriptional profile. Further analyses of HSCs and macrophage subpopulations and ligand-receptor interaction revealed a high heterogeneity characterization and tightly interregulated network of these two groups of cells in liver fibrosis. Finally, we uncovered a profibrotic Thbs1+ macrophage subcluster, which expands in mouse and human fibrotic livers, activating HSCs via PI3K/AKT/mTOR signaling pathway. Our findings decode unanticipated insights into the heterogeneity of HSCs and macrophages and their intercellular crosstalk at a single-cell level, and may provide potential therapeutic strategies in liver fibrosis.© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

基金：
National Natural Science Foundation of China, Grant/Award Numbers: 82002495, 82070634, 81702333; Research Fund of Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology, Grant/Award Numbers: ZDSYS-2020-04, ZDSYS-2020-02; Shanghai Jiao Tong University Cross Disciplinary Translational Foundation, Grant/Award Number: ZH2018ZDA33
语种：
外文
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出版当年[2022]版：
无
最新[2023]版：
大类 | 3 区 医学
小类 | 3 区 医学：研究与实验
JCR分区：
出版当年[2021]版：
无
最新[2023]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2]Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2]Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [4]Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China [7]eHealth Program of Shanghai Anti-Doping Laboratory, Shanghai University of Sport, Shanghai, China [8]Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [*1]Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China. [*2]Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200236, China. [*3]Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
推荐引用方式(GB/T 7714)：
Cheng Sheng,Zou Yunhan,Zhang Man,et al.Single-cell RNA sequencing reveals the heterogeneity and intercellular communication of hepatic stellate cells and macrophages during liver fibrosis[J].MEDCOMM.2023,4(5):doi:10.1002/mco2.378.
APA：
Cheng Sheng,Zou Yunhan,Zhang Man,Bai Shihao,Tao Kun...&Han Bo.(2023).Single-cell RNA sequencing reveals the heterogeneity and intercellular communication of hepatic stellate cells and macrophages during liver fibrosis.MEDCOMM,4,(5)
MLA：
Cheng Sheng,et al."Single-cell RNA sequencing reveals the heterogeneity and intercellular communication of hepatic stellate cells and macrophages during liver fibrosis".MEDCOMM 4..5(2023)

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