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Volume 44 Issue 3
May  2023
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Article Navigation >  Zoological Research  > 2023  >  44(3): 451-466
Peng-Cheng Guo, Jing Zuo, Ke-Ke Huang, Guang-Yao Lai, Xiao Zhang, Juan An, Jin-Xiu Li, Li Li, Liang Wu, Yi-Ting Lin, Dong-Ye Wang, Jiang-Shan Xu, Shi-Jie Hao, Yang Wang, Rong-Hai Li, Wen Ma, Yu-Mo Song, Chang Liu, Chuan-Yu Liu, Zhen Dai, Yan Xu, Amar Deep Sharma, Michael Ott, Qing Ou-Yang, Feng Huo, Rong Fan, Yong-Yin Li, Jin-Lin Hou, Giacomo Volpe, Long-Qi Liu, Miguel A. Esteban, Yi-Wei Lai. Cell atlas of CCl4-induced progressive liver fibrosis reveals stage-specific responses. Zoological Research, 2023, 44(3): 451-466. doi: 10.24272/j.issn.2095-8137.2023.031
Citation: Peng-Cheng Guo, Jing Zuo, Ke-Ke Huang, Guang-Yao Lai, Xiao Zhang, Juan An, Jin-Xiu Li, Li Li, Liang Wu, Yi-Ting Lin, Dong-Ye Wang, Jiang-Shan Xu, Shi-Jie Hao, Yang Wang, Rong-Hai Li, Wen Ma, Yu-Mo Song, Chang Liu, Chuan-Yu Liu, Zhen Dai, Yan Xu, Amar Deep Sharma, Michael Ott, Qing Ou-Yang, Feng Huo, Rong Fan, Yong-Yin Li, Jin-Lin Hou, Giacomo Volpe, Long-Qi Liu, Miguel A. Esteban, Yi-Wei Lai. Cell atlas of CCl4-induced progressive liver fibrosis reveals stage-specific responses. Zoological Research, 2023, 44(3): 451-466. doi: 10.24272/j.issn.2095-8137.2023.031
shu

Cell atlas of CCl4-induced progressive liver fibrosis reveals stage-specific responses

doi: 10.24272/j.issn.2095-8137.2023.031
  • 1.

    State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China

  • 2.

    BGI-Hangzhou, Hangzhou, Zhejiang 310012, China

  • 3.

    BGI-Shenzhen, Shenzhen, Guangdong 518083, China

  • 4.

    Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510799, China

  • 5.

    Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China

  • 6.

    Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health and Guangzhou Medical University, Guangzhou, Guangdong 510530, China

  • 7.

    School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China

  • 8.

    College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China

  • 9.

    Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China

  • 10.

    Biotherapy Centre, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China

  • 11.

    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover 30625, Germany

  • 12.

    Department of Hepatobiliary Surgery and Liver Transplant Center, General Hospital of Southern Theater Command, Guangzhou, Guangdong 510010, China

  • 13.

    Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangzhou, Guangdong 510515, China

  • 14.

    Hematology and Cell Therapy Unit, IRCCS-Istituto Tumori ‘Giovanni Paolo II’, Bari 70124, Italy

  • 15.

    Institute of Experimental Hematology, Hannover Medical School, Hannover 30625, Germany

All raw data generated in this study have been deposited to the CNGB Nucleotide Sequence Archive under accession code CNP0003569. All processed data can be accessed at Science Data Bank with the link https://doi.org/10.57760/sciencedb.j00139.00049 or Open Archive for Miscellaneous Data in Genome Sequence Archive under accession code OMIX003436.
The authors declare that they have no competing interests.
P.C.G., M.A.E., and Y.W.L. conceived the idea; M.A.E. and Y.W.L. supervised the work; P.C.G. and Y.W.L. designed the experiments; P.C.G. performed most of the experiments with the help of K.K.H.; P.C.G., J.Z., and Y.W.L. analyzed the data; G.Y.L., X.Z., J.A., J.X.L., L.L., L.W., Y.T.L., D.Y.W., J.S.X., S.J.H., Y.W., R.H.L., W.M., Y.M.S., C.L., and C.Y.L. provided technical support; Z.D., Y.X., A.D.S., M.O., Q.O.Y., F.H., R.F., Y.Y.L., J.L.H., G.V., and L.Q.L. gave relevant advice; M.A.E. and Y.W.L. wrote the manuscript. All authors read and approved the final version of the manuscript.
#Authors contributed equally to this work
Funds:  This work was supported by the National Natural Science Foundation of China (32200688, 92068106, U20A2015, 32211530050), Guangdong Basic and Applied Basic Research Foundation (2021B1515120075, 2021A1515110180), and Science and Technology Program of Guangzhou (202201010408, 202201011037)
More Information
    Abstract
  • Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis, a major cause of morbidity and mortality worldwide. However, there are currently no effective anti-fibrotic therapies available, especially for late-stage patients, which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cell-specific responses in different fibrosis stages. To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes, we generated a single-nucleus transcriptomic atlas encompassing 49 919 nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride (CCl4)-induced progressive liver fibrosis. Integrative analysis distinguished the sequential responses to injury of hepatocytes, hepatic stellate cells and endothelial cells. Moreover, we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes. These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions, dysfunction for clearance by apoptosis of activated hepatic stellate cells, accumulation of pro-fibrotic signals, and the switch from an anti-angiogenic to a pro-angiogenic program during CCl4-induced progressive liver fibrosis. Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.
    • All raw data generated in this study have been deposited to the CNGB Nucleotide Sequence Archive under accession code CNP0003569. All processed data can be accessed at Science Data Bank with the link https://doi.org/10.57760/sciencedb.j00139.00049 or Open Archive for Miscellaneous Data in Genome Sequence Archive under accession code OMIX003436.
    The authors declare that they have no competing interests.
    P.C.G., M.A.E., and Y.W.L. conceived the idea; M.A.E. and Y.W.L. supervised the work; P.C.G. and Y.W.L. designed the experiments; P.C.G. performed most of the experiments with the help of K.K.H.; P.C.G., J.Z., and Y.W.L. analyzed the data; G.Y.L., X.Z., J.A., J.X.L., L.L., L.W., Y.T.L., D.Y.W., J.S.X., S.J.H., Y.W., R.H.L., W.M., Y.M.S., C.L., and C.Y.L. provided technical support; Z.D., Y.X., A.D.S., M.O., Q.O.Y., F.H., R.F., Y.Y.L., J.L.H., G.V., and L.Q.L. gave relevant advice; M.A.E. and Y.W.L. wrote the manuscript. All authors read and approved the final version of the manuscript.
    #Authors contributed equally to this work
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