Single-cell RNA sequencing reveals the landscape of the cellular ecosystem of primary hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) cells, along with multiple nonmalignant stromal cells, such as fibroblasts, endothelial cells and immune cells, comprise an intricate cellular ecosystem, undergo dynamic phenotypic changes and present complicated cellular interactions, thus synergistically facilitating HCC initiation and progression and leading to treatment resistance. Clarifying the heterogeneity, cell plasticity and complexity of the cellular ecosystem of HCC will be highly beneficial for understanding HCC development and identifying novel therapeutic targets. Single-cell RNA sequencing (scRNA-seq) refers to profiling the transcriptome at single-cell resolution, and the development of scRNA-seq technology and analysis algorithms has greatly promoted the analysis of cell composition, cell subpopulation heterogeneity, development trajectory and cell-to-cell interactions in cell populations. In this review, we systematically summarized and discussed scRNA-seq in treatment-naive primary HCC and revealed the global cell composition of HCC; the widespread molecular heterogeneity of HCC cells; the molecular subtypes of fibroblasts; the cell composition, functional states and development trajectory of immune cells; and the frequent interactions between different cell types to systematically draw the landscape of the cellular ecosystem of primary HCC.