Single-cell transcriptome sequencing reveals tumor stem cells and their molecular characteristics in intrahepatic cholangiocarcinoma.

Intercellular communication signals in the tumor microenvironment are closely related to behaviors such as cancer cell proliferation and immune evasion. However, the specific roles of intercellular signaling pathways in intrahepatic cholangiocarcinoma (ICC) have not yet been fully characterized. In this study, we analyzed publicly available single-cell RNA sequencing (scRNA-seq) data derived from paired samples of two intrahepatic cholangiocarcinoma (ICC) tissues and two adjacent normal tissues, thoroughly examining their cellular composition. InferCNV analysis was employed to compare tumor cells and normal cells, and pseudotime analysis was used to identify the growth and differentiation trajectories of the cells. Additionally, intercellular communication analysis was conducted to elucidate the communication networks between cells. Our analysis delineated the cellular ecosystem of ICC, identifying cell subclusters with shared characteristics between ICC and normal tissues. Notably, we characterized a distinct C7-E-T subcluster that exhibited high expression of CXCR4 and BPTF, markers associated with cancer stem cells (CSCs). Further investigation revealed that the MIF intercellular signaling pathway promotes the progression of ICC by activating intracellular signals in the MYC pathway. This study highlights the dysregulation of intercellular signaling pathways within tumor clusters, which influences the onset and progression of ICC. The cancer stem cell subpopulation (CXCR4hiBPTFhiE-T) exerts a significant influence on ICC progression by secreting relevant signaling molecules via the MIF signaling pathway.