机构：[1]Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai 201203, Peoples R China[2]Naval Med Univ, Changzheng Hosp, Dept Colorectal Surg, Shanghai, Peoples R China[3]Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Dept Dermatol, Shanghai, Peoples R China[4]Naval Med Univ, Changzheng Hosp, Dept Pathol, Shanghai, Peoples R China[5]Naval Med Univ, Changhai Hosp, Dept Pathol, Shanghai, Peoples R China[6]Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Plant Dev, Beijing, Peoples R China[7]Naval Med Univ, Sch Pharm, Shanghai, Peoples R China
BackgroundMucinous colorectal adenocarcinoma (MCA) is a distinct subtype of colorectal cancer (CRC) with the most aggressive pattern, but effective treatment of MCA remains a challenge due to its vague pathological characteristics. An in-depth understanding of transcriptional dynamics at the cellular level is critical for developing specialised MCA treatment strategies.MethodsWe integrated single-cell RNA sequencing and spatial transcriptomics data to systematically profile the MCA tumor microenvironment (TME), particularly the interactome of stromal and immune cells. In addition, a three-dimensional bioprinting technique, canonical ex vivo co-culture system, and immunofluorescence staining were further applied to validate the cellular communication networks within the TME.ResultsThis study identified the crucial intercellular interactions that engaged in MCA pathogenesis. We found the increased infiltration of FGF7+/THBS1+ myofibroblasts in MCA tissues with decreased expression of genes associated with leukocyte-mediated immunity and T cell activation, suggesting a crucial role of these cells in regulating the immunosuppressive TME. In addition, MS4A4A+ macrophages that exhibit M2-phenotype were enriched in the tumoral niche and high expression of MS4A4A+ was associated with poor prognosis in the cohort data. The ligand-receptor-based intercellular communication analysis revealed the tight interaction of MUC1+ malignant cells and ZEB1+ endothelial cells, providing mechanistic information for MCA angiogenesis and molecular targets for subsequent translational applications.ConclusionsOur study provides novel insights into communications among tumour cells with stromal and immune cells that are significantly enriched in the TME during MCA progression, presenting potential prognostic biomarkers and therapeutic strategies for MCA.Key points Tumour microenvironment profiling of MCA is developed. MUC1+ tumour cells interplay with FGF7+/THBS1+ myofibroblasts to promote MCA development. MS4A4A+ macrophages exhibit M2 phenotype in MCA. ZEB1+ endotheliocytes engage in EndMT process in MCA. (1) Tumor microenvironment profiling of MCA is developed. (2) MUC1+ tumour cells interplay with FGF7+/THBS1+ myofibroblasts to promote MCA development. (3) MS4A4A+ macrophages exhibit M2 phenotype in MCA. (4) ZEB1+ endotheliocytes engage in the EndMT process in MCA. image
基金：
National Natural Science Foundation of China; National Key R&D Program of China [2019YFA0110601, 2022YFC3502000]; Oriental Scholars of Shanghai [TP2022081]; Young Talent Lifting Project of China Association of Chinese Medicine [2021-QNRC2-A08]; Shanghai Science and Technology Innovation Action Plan [21S11902800]; Shanghai Rising-Star Program [22QA1409100]; Thousand Talents Plan of Jiangxi Province [jxsq2023102168]; Three-year Action Plan for Shanghai TCM Development and Inheritance Program [(2021-2023)-0208, (2021-2023)-0401]; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine [ZYYCXTD-D-202004]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2023-I2M-3-009]; Innovation team of high-level local universities in Shanghai: Strategic Innovation Team of TCM Chemical Biology; OE Biotech; [82173846]; [82322073]; [81571827]; [82374086]
第一作者机构：[1]Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai 201203, Peoples R China[2]Naval Med Univ, Changzheng Hosp, Dept Colorectal Surg, Shanghai, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai 201203, Peoples R China[6]Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Plant Dev, Beijing, Peoples R China[7]Naval Med Univ, Sch Pharm, Shanghai, Peoples R China
推荐引用方式(GB/T 7714)：
Zhou Haiyang,Shen Yiwen,Zheng Guangyong,et al.Integrating single-cell and spatial analysis reveals MUC1-mediated cellular crosstalk in mucinous colorectal adenocarcinoma[J].CLINICAL AND TRANSLATIONAL MEDICINE.2024,14(5):doi:10.1002/ctm2.1701.
APA：
Zhou, Haiyang,Shen, Yiwen,Zheng, Guangyong,Zhang, Beibei,Wang, Anqi...&Zhang, Weidong.(2024).Integrating single-cell and spatial analysis reveals MUC1-mediated cellular crosstalk in mucinous colorectal adenocarcinoma.CLINICAL AND TRANSLATIONAL MEDICINE,14,(5)
MLA：
Zhou, Haiyang,et al."Integrating single-cell and spatial analysis reveals MUC1-mediated cellular crosstalk in mucinous colorectal adenocarcinoma".CLINICAL AND TRANSLATIONAL MEDICINE 14..5(2024)
