A_single_cell_RNA_seq_approach_to_define_the_key_pro_fibrogenic_cells_in_liver_fibrosis___Mouse

Single cell RNA sequencing is transforming the way we think about disease pathogenesis, and allows the interrogation of individual pathogenic cell subpopulations with unprecedented resolution. Resident hepatic mesenchymal cells, which are the major source of scar deposition during liver fibrogenesis, have long been regarded as a functionally homogeneous population following liver injury. However, using a single cell RNAseq approach (SmartSeq2 protocol) in mouse models of hepatic fibrosis, we have found that the hepatic mesenchyme is comprised of multiple different cellular subpopulations, with highly variable pro-fibrotic phenotypes. In this project we will use a droplet-based, high throughput single cell sequencing platform (10X Genomics) to interrogate the transcriptomes of thousands of mesenchymal cells from mouse models of liver fibrosis and also from normal and cirrhotic human livers. Critically, this high throughput approach will allow the identification of the key profibrogenic subpopulations driving human liver fibrosis with a very high degree of resolution, and will allow the identification of new, rational anti-fibrotic targets to treat patients with chronic liver disease.