Integrating spatial and single-cell transcriptomics reveals tumor heterogeneity and intercellular networks in colorectal cancer.

Autor: Xiao J; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai, Guangdong, China.; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China., Yu X; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai, Guangdong, China., Meng F; CapitalBio Technology Corporation, Beijing, China., Zhang Y; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai, Guangdong, China., Zhou W; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai, Guangdong, China., Ren Y; CapitalBio Technology Corporation, Beijing, China., Li J; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai, Guangdong, China., Sun Y; CapitalBio Technology Corporation, Beijing, China., Sun H; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai, Guangdong, China., Chen G; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China. guokaichen@um.edu.mo.; Zhuhai UM Science & Technology Research Institute, Zhuhai, Guangdong, China. guokaichen@um.edu.mo., He K; Minimally Invasive Tumor Therapies Center, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China. hiker00006@126.com., Lu L; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai, Guangdong, China. luligong1969@jnu.edu.cn.; Guangzhou First People's Hospital, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China. luligong1969@jnu.edu.cn.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2024 May 10; Vol. 15 (5), pp. 326. Date of Electronic Publication: 2024 May 10.
DOI: 10.1038/s41419-024-06598-6
Abstrakt: Single cell RNA sequencing (scRNA-seq), a powerful tool for studying the tumor microenvironment (TME), does not preserve/provide spatial information on tissue morphology and cellular interactions. To understand the crosstalk between diverse cellular components in proximity in the TME, we performed scRNA-seq coupled with spatial transcriptomic (ST) assay to profile 41,700 cells from three colorectal cancer (CRC) tumor-normal-blood pairs. Standalone scRNA-seq analyses revealed eight major cell populations, including B cells, T cells, Monocytes, NK cells, Epithelial cells, Fibroblasts, Mast cells, Endothelial cells. After the identification of malignant cells from epithelial cells, we observed seven subtypes of malignant cells that reflect heterogeneous status in tumor, including tumor_CAV1, tumor_ATF3_JUN | FOS, tumor_ZEB2, tumor_VIM, tumor_WSB1, tumor_LXN, and tumor_PGM1. By transferring the cellular annotations obtained by scRNA-seq to ST spots, we annotated four regions in a cryosection from CRC patients, including tumor, stroma, immune infiltration, and colon epithelium regions. Furthermore, we observed intensive intercellular interactions between stroma and tumor regions which were extremely proximal in the cryosection. In particular, one pair of ligands and receptors (C5AR1 and RPS19) was inferred to play key roles in the crosstalk of stroma and tumor regions. For the tumor region, a typical feature of TMSB4X-high expression was identified, which could be a potential marker of CRC. The stroma region was found to be characterized by VIM-high expression, suggesting it fostered a stromal niche in the TME. Collectively, single cell and spatial analysis in our study reveal the tumor heterogeneity and molecular interactions in CRC TME, which provides insights into the mechanisms underlying CRC progression and may contribute to the development of anticancer therapies targeting on non-tumor components, such as the extracellular matrix (ECM) in CRC. The typical genes we identified may facilitate to new molecular subtypes of CRC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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