Understanding initiation and progression of hepatocellular carcinoma through single cell sequencing

Unsatisfied clinical outcome drives to better understand hepatic carcinogenesis, microenvironment and escape of immune surveillance in hepatocellular carcinoma (HCC). Single cell RNA sequencing (scRNA-Seq) has generated enormous data to pinpoint pathophysiologic alterations in tumor microenvironment (TME) or trace lineage development in cancer stem cells (CSCs), circulating tumor cells (CTCs), and subsets of immune cells, such as exhausting T cells, tumor-associated macrophages (TAMs), dendritic cells or other lineages. New insights have significantly advanced current understanding in progression, poor responses to molecular-targeted therapeutics or immune checkpoint inhibitors, metastasis in both basic research and clinical practice. The present review intends to cover a basic workflow of the scRNA-seq technology, existing limitations and improvement areas. Moreover, in-depth understanding in TME, exhausting T cells, CSCs, CTCs, tumor-associated macrophages, dendritic cells in HCC facilitates implementation of personalized and precise therapy in an era of availability with an array of systemic regimens.