biostudies-literatureUnknown13(1)Qi JColorectal cancer (CRC) is among the most common malignancies with limited treatments other than surgery. The tumor microenvironment (TME) profiling enables the discovery of potential therapeutic targets. Here, we profile 54,103 cells from tumor and adjacent tissues to characterize cellular composition and elucidate the potential origin and regulation of tumor-enriched cell types in CRC. We demonstrate that the tumor-specific FAP⁺ fibroblasts and SPP1⁺ macrophages were positively correlated in 14 independent CRC cohorts containing 2550 samples and validate their close localization by immuno-fluorescent staining and spatial transcriptomics. This interaction might be regulated by chemerin, TGF-β, and interleukin-1, which would stimulate the formation of immune-excluded Nature communications1742https://www.ebi.ac.uk/biostudies/studies/S-EPMC8976074biostudies-literatureSingle-cell and spatial analysis reveal interaction of FAP⁺ fibroblasts and SPP1⁺ macrophages in colorectal cancer.PMC8976074Hong LLiu HSu BQi JLiu LXun ZHan LFang FChen LZou DYe YBao RLiu YDing XGinhoux FLi ZZhang YJia WSun HZhong JWang ZfalseSingle-cell and spatial analysis reveal interaction of FAP⁺ fibroblasts and SPP1⁺ macrophages in colorectal cancer.Colorectal cancer (CRC) is among the most common malignancies with limited treatments other than surgery. The tumor microenvironment (TME) profiling enables the discovery of potential therapeutic targets. Here, we profile 54,103 cells from tumor and adjacent tissues to characterize cellular composition and elucidate the potential origin and regulation of tumor-enriched cell types in CRC. We demonstrate that the tumor-specific FAP⁺ fibroblasts and SPP1⁺ macrophages were positively correlated in 14 independent CRC cohorts containing 2550 samples and validate their close localization by immuno-fluorescent staining and spatial transcriptomics. This interaction might be regulated by chemerin, TGF-β, and interleukin-1, which would stimulate the formation of immune-excluded 2022-01-01T00:00:00Z2022 Apr2025-04-04T19:41:21.95Z2025-04-04T19:41:21.95ZS-EPMC89760743536562910.1038/s41467-022-29366-6