Single-cell and spatial transcriptome analysis reveals the cellular heterogeneity of liver metastatic colorectal cancer

Author:

Wang Fei12ORCID,Long Jie1ORCID,Li Liang2ORCID,Wu Zi-Xin3,Da Tian-Tian4,Wang Xiao-Qing4,Huang Chuan4,Jiang Yi-Hua1,Yao Xue-Qing5,Ma Hai-Qing2ORCID,Lian Zhe-Xiong16ORCID,Zhao Zhi-Bin2ORCID,Cao Jie3ORCID

Affiliation:

1. Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.

2. Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.

3. Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510080, China.

4. School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China.

5. Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.

6. Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.

Abstract

In this study, we comprehensively charted the cellular landscape of colorectal cancer (CRC) and well-matched liver metastatic CRC using single-cell and spatial transcriptome RNA sequencing. We generated 41,892 CD45 nonimmune cells and 196,473 CD45 + immune cells from 27 samples of six CRC patients, and found that CD8_CXCL13 and CD4_CXCL13 subsets increased significantly in liver metastatic samples that exhibited high proliferation ability and tumor-activating characterization, contributing to better prognosis of patients. Distinct fibroblast profiles were observed in primary and liver metastatic tumors. F3 + fibroblasts enriched in primary tumors contributed to worse overall survival by expressing protumor factors. However, MCAM + fibroblasts enriched in liver metastatic tumors might promote generation of CD8_CXCL13 cells through Notch signaling. In summary, we extensively analyzed the transcriptional differences of cell atlas between primary and liver metastatic tumors of CRC by single-cell and spatial transcriptome RNA sequencing, providing different dimensions of the development of liver metastasis in CRC.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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