Integrating single‐cell and spatial analysis reveals MUC1‐mediated cellular crosstalk in mucinous colorectal adenocarcinoma

作者：Haiyang Zhou, Yiwen Shen, Guangyong Zheng, Beibei Zhang, Anqi Wang, Jing Zhang, Hao Hu, Jiayi Lin, Sanhong Liu, Xin Luan, Weidong Zhang · 发表于：Clinical and Translational Medicine · 年份：2024 · DOI：10.1002/ctm2.1701 · 被引用次数：15 · 研究领域：Single-cell and spatial transcriptomics、Cancer Cells and Metastasis、Angiogenesis and VEGF in Cancer

Abstract Background Mucinous 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. Methods We 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. Results This 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...