Single-cell transcriptomics uncovers zonation of function in the mesenchyme during liver fibrosis

We profile the transcriptomes of ~30,000 mouse single cells to deconvolve the hepatic mesenchyme in healthy and fibrotic liver at high resolution. We reveal spatial zonation of hepatic stellate cells across the liver lobule, designated portal vein-associated HSC and central vein-associated HSC, and uncover an equivalent functional zonation in a mouse model of centrilobular fibrosis. Our work illustrates the power of single-cell transcriptomics to resolve key collagen-producing cells driving liver fibrosis with high precision. Single-cell transcriptomic data (10x and SS2) are presented from both healthy mice and following carbon tetrachloride administration (acute (72h) and chronic (6wk) injury models). SS2 data also contains cells harvested from mice 14d post bile duct ligation.