Comprehensive Analysis of Cellular Heterogeneity and Transcriptional Regulation in the Tumor Microenvironment of Hepatocellular Carcinoma

• Single-cell RNA sequencing reveals extensive intratumoral heterogeneity in hepatocellular carcinoma, with multiple malignant cell subpopulations exhibiting distinct transcriptional programs. • A specific cancer-associated fibroblast (CAF) subset with high matrix remodeling activity is associated with poor clinical outcomes. • Cell-cell communication analysis uncovers TGF-β and CXCL signaling as key mediators of immunosuppressive crosstalk in the tumor microenvironment. • Integration of transcriptomic data identifies candidate transcription factors and therapeutic targets that may be exploited for precision oncology.