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A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma

Author

Listed:
  • Yiming Lu

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine)

  • Aiqing Yang

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine)

  • Cheng Quan

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine)

  • Yingwei Pan

    (Chinese PLA General Hospital)

  • Haoyun Zhang

    (Chinese PLA General Hospital)

  • Yuanfeng Li

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine)

  • Chengming Gao

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine)

  • Hao Lu

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine)

  • Xueting Wang

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
    Hebei University)

  • Pengbo Cao

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine)

  • Hongxia Chen

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine)

  • Shichun Lu

    (Chinese PLA General Hospital)

  • Gangqiao Zhou

    (State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
    Nanjing Medical University)

Abstract

Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. Here, we generate a single-cell atlas of the multicellular ecosystem of HCC from four tissue sites. We show the enrichment of central memory T cells (TCM) in the early tertiary lymphoid structures (E-TLSs) in HCC and assess the relationships between chronic HBV/HCV infection and T cell infiltration and exhaustion. We find the MMP9+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and PPARγ to be the pivotal transcription factor driving their differentiation. We also characterize the heterogeneous subpopulations of malignant hepatocytes and their multifaceted functions in shaping the immune microenvironment of HCC. Finally, we identify seven microenvironment-based subtypes that can predict prognosis of HCC patients. Collectively, this large-scale atlas deepens our understanding of the HCC microenvironment, which might facilitate the development of new immune therapy strategies for this malignancy.

Suggested Citation

  • Yiming Lu & Aiqing Yang & Cheng Quan & Yingwei Pan & Haoyun Zhang & Yuanfeng Li & Chengming Gao & Hao Lu & Xueting Wang & Pengbo Cao & Hongxia Chen & Shichun Lu & Gangqiao Zhou, 2022. "A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32283-3
    DOI: 10.1038/s41467-022-32283-3
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    1. Justin I. Odegaard & Roberto R. Ricardo-Gonzalez & Matthew H. Goforth & Christine R. Morel & Vidya Subramanian & Lata Mukundan & Alex Red Eagle & Divya Vats & Frank Brombacher & Anthony W. Ferrante & , 2007. "Macrophage-specific PPARγ controls alternative activation and improves insulin resistance," Nature, Nature, vol. 447(7148), pages 1116-1120, June.
    2. Lei Zhang & Xin Yu & Liangtao Zheng & Yuanyuan Zhang & Yansen Li & Qiao Fang & Ranran Gao & Boxi Kang & Qiming Zhang & Julie Y. Huang & Hiroyasu Konno & Xinyi Guo & Yingjiang Ye & Songyuan Gao & Shan , 2018. "Lineage tracking reveals dynamic relationships of T cells in colorectal cancer," Nature, Nature, vol. 564(7735), pages 268-272, December.
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    Cited by:

    1. Delilah Hendriks & Benedetta Artegiani & Thanasis Margaritis & Iris Zoutendijk & Susana Chuva de Sousa Lopes & Hans Clevers, 2024. "Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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