Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment

被引：18

作者：

Xie, Zhenyu ^{[1
]}

Niu, Liaoran ^{[1
]}

Zheng, Gaozan ^{[1
]}

Du, Kunli ^{[1
]}

Dai, Songchen ^{[2
,3
]}

Li, Ruikai ^{[1
]}

Dan, Hanjun ^{[1
]}

Duan, Lili ^{[1
]}

Wu, Hongze ^{[1
]}

Ren, Guangming ^{[4
]}

Dou, Xinyu ^{[4
]}

Feng, Fan ^{[1
]}

Zhang, Jian ^{[5
]}

Zheng, Jianyong ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp, Dept Gastrointestinal Surg, State Key Lab Canc Biol, 169 Changle Rd, Xian 710032, Shaanxi, Peoples R China

[2] China Med Univ, Hosp 1, Dept Surg Oncol & Gen Surg, Shenyang 110016, Peoples R China

[3] Minist Educ, Key Lab Precis Diag & Treatment Gastrointestinal T, Shenyang 110016, Peoples R China

[4] Xian Med Univ, Xian 710021, Shaanxi, Peoples R China

[5] Fourth Mil Med Univ, Dept Biochem & Mol Biol, State Key Lab Canc Biol, 169 Changle Rd, Xian 710032, Shaanxi, Peoples R China

来源：

CELL AND BIOSCIENCE | 2023年 / 13卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Mast cells; Colorectal cancer; Heterogeneity; Activation; Single-cell analysis; Prognosis; MISMATCH REPAIR STATUS; PROGNOSTIC-SIGNIFICANCE; DENSITY; SURVIVAL;

D O I：

10.1186/s13578-023-01144-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The role of mast cells (MCs) in colorectal cancer (CRC) remains unclear, and a comprehensive single-cell study on CRC MCs has not been conducted. This study used a multi-omics approach, integrating single-cell sequencing, spatial transcriptomics, and bulk tissue sequencing data to investigate the heterogeneity and impact of MCs in CRC. Five MC signature genes (TPSAB1, TPSB2, CPA3, HPGDS, and MS4A2) were identified, and their average expression was used as a marker of MCs. The MC density was found to be lower in CRC compared to normal tissue, but MCs in CRC demonstrated distinct activation features. Activated MCs were defined by high expression of receptors and MC mediators, while resting MCs had low expression. Most genes, including the five MC signature genes, were expressed at higher levels in activated MCs. The MC signature was linked to a better prognosis in both CRC and pan-cancer patient cohorts. Elevated KITLG expression was observed in fibroblasts and endothelial cells in CRC samples compared to normal tissue, and co-localization of MCs with these cell types was revealed by spatial transcriptome analysis. In conclusion, this study finds decreased MC density in CRC compared to normal tissue, but highlights a shift in MC phenotype from CMA1high resting cells to activated TPSAB1high, CPA3high, and KIThigh cells. The elevated KITLG expression in the tumor microenvironment's fibroblasts and endothelial cells may activate MCs through the KITLG-KIT axis, potentially suppressing tumor progression.

引用

页数：17

共 54 条

[31] Single-cell RNA sequencing of mast cells in eosinophilic esophagitis reveals heterogeneity, local proliferation, and activation that persists in remission [J].