Investigation of pro-regenerative mesenchymal subpopulations during liver regeneration using a single cell RNA sequencing approach (360G-Wellcome-209876_Z_17_Z)

Chronic liver disease (CLD) is a major cause of morbidity and mortality worldwide. The liver has a remarkable ability to regenerate following injury, however in many cases of CLD this regenerative capacity is overwhelmed. Currently the only effective treatment is liver transplantation but demand for donor organs greatly outstrips supply. New therapies are urgently required. Liver regeneration involves a complex interplay between multiple cell types, including a family of cells called mesenchymal cells. Whilst traditionally, the role of mesenchymal cells was more often studied in the context of liver fibrosis (scarring), recent studies have shown that these cells are also important during liver regeneration. Initial experiments in the Henderson lab, using a cutting-edge technology called single cell RNA sequencing (which allows the sequencing of genes in single cells), has shown that mesenchymal cells, rather than being one family of cells with similar function, are actually very varied in terms of their function, performing many different, important roles within the liver. I will use this powerful technique to identify the pro-regenerative mesenchymal cell subpopulations responsible for driving liver regeneration. Using this information, we hope to design new treatments to harness specific cellular subsets to drive liver regeneration in patients with CLD.