Hepatic stellate cells in physiology and pathology

Hepatic stellate cells (HSCs) comprise a minor cell population in the liver but serve numerous critical functions in the normal liver and in response to injury. HSCs are primarily known for their activation upon liver injury and for producing the collagen-rich extracellular matrix in liver fibrosis. In the absence of liver injury, HSCs reside in a quiescent state, in which their main function appears to be the storage of retinoids or vitamin A-containing metabolites. Less appreciated functions of HSCs include amplifying the hepatic inflammatory response and expressing growth factors that are critical for liver development and both the initiation and termination of liver regeneration. Recent single-cell RNA sequencing studies have corroborated earlier studies indictaing that HSC activation involves a diverse array of phenotypic alterations and identified unique HSC populations. This review serves to highlight these many functions of HSCs, and to briefly describe the recent genetic tools that will help to thoroughly investigate the role of HSCs in hepatic physiology and pathology.