Volume 44 Issue 3
May  2023
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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

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

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