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However, the high tumor heterogeneity of ICC restricts the efficacy of available systematic therapies. We aim to dissect the tumor heterogeneity of ICC utilizing high\u2010resolution single\u2010cell RNA sequencing to identify novel therapeutic targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed single\u2010cell RNA sequencing (scRNA\u2010seq) of 26 tumor samples from 23 ICC patients and spatial transcriptomic sequencing of six tumor sections from six ICC patients. Bulk RNA\u2010seq data from two public datasets were used for validation. Additionally, immunohistochemical staining and multiplex immunofluorescence staining were conducted to validate the infiltration and distribution of cells in the tumor microenvironment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We discovered that malignant cells in ICC samples exhibited a remarkably high degree of tumor heterogeneity. We identified a basal\u2010like tumor cell subpopulation characterized by the expression of basal epithelial related genes including KRT5, KRT6A, and KRT17. The basal\u2010like tumor subpopulation was characterized by activation of MET signaling and extracellular matrix organization associated with tumor invasion and correlated with poor prognosis. Cell\u2013cell communication analysis further showed significant HGF\u2010MET interaction between inflammatory cancer\u2013associated fibroblasts (iCAFs) and basal\u2010like tumor cells. We found that iCAFs were the major source of HGF in tumor environment and contributed to the basal\u2010like phenotype formation of tumor cells by HGF\u2010MET axis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified an aggressive basal\u2010like tumor cell subpopulation, which correlated with poor prognosis in ICC. The MET pathway contributes to the aggressiveness of basal\u2010like tumor cells and serves as a novel therapeutic target for ICC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.16915","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T22:43:16Z","timestamp":1741732996000},"page":"1263-1273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Single\u2010Cell Transcriptomic Analysis Reveals an Aggressive Basal\u2010Like Tumor Cell Subpopulation Associated With Poor Prognosis in Intrahepatic Cholangiocarcinoma"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7390-4372","authenticated-orcid":false,"given":"Changyi","family":"Liao","sequence":"first","affiliation":[{"name":"Cancer Center, The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong 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