Single cell-spatial transcriptomics and bulk multi-omics analysis of heterogeneity and ecosystems in hepatocellular carcinoma
This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.
Authors
- Zhiling Liao
- Xi Huang (ORCID: https://orcid.org/0000-0002-6871-4099)
- Rong Liang (ORCID: https://orcid.org/0000-0003-0343-3277)
- Cheng Lu (ORCID: https://orcid.org/0000-0002-7651-3924)
- Feixiang Wu
- Julu Huang
- Shilin Huang (ORCID: https://orcid.org/0000-0003-4215-9151)
- Lequn Li
- Min Luo (ORCID: https://orcid.org/0000-0001-5732-4848)
- Yan Lin (ORCID: https://orcid.org/0000-0002-0585-6671)
- Guobin Wu (ORCID: https://orcid.org/0000-0003-0505-9637)
- Xing Gao (ORCID: https://orcid.org/0000-0001-8893-2416)
- Bang‐De Xiang (ORCID: https://orcid.org/0000-0002-2758-1437)
- Jiazhou Ye (ORCID: https://orcid.org/0000-0001-9124-7284)
- Jie Chen (ORCID: https://orcid.org/0000-0001-7925-3729)
- Lu Lu (ORCID: https://orcid.org/0000-0002-9457-0164)
- Yongqiang Li (ORCID: https://orcid.org/0000-0001-6426-4011)
- Xiaoling Luo (ORCID: https://orcid.org/0009-0004-9640-7899)
- Hongping Yu (ORCID: https://orcid.org/0000-0001-9851-2351)
- Tao Bai (ORCID: https://orcid.org/0000-0002-0569-8183)
- Mingzhi Xie
- Xiaobo Wang (ORCID: https://orcid.org/0009-0003-0759-0592)
- Jinyan Zhang (ORCID: https://orcid.org/0009-0001-2001-1773)
- Liang Ma
Institutions
- Guangxi Medical University (CN)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2024-11-15
- DOI
- https://doi.org/10.1038/s41698-024-00752-1
- Citations
- 27
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 6.31
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangxi Province
- Guangxi Medical University