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

Fei WangJie LongLiang LiZi-Xin WuTian-Tian DaXiao-Qing WangChuan HuangYi-Hua JiangXue-Qing YaoHai-Qing MaZhe-Xiong LianZhi-Bin ZhaoJie Cao
Published in: Science advances (2023)
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.
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