Journal
CELL REPORTS
Volume 29, Issue 7, Pages 1832-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.10.024
Keywords
-
Categories
Funding
- Wellcome Trust [103749]
- Guts UK-Children's Liver Disease Foundation [R43927]
- Tenovus Scotland grant [E18/05]
- MRC Clinician Scientist Fellowship [MR/N008340/1]
- UK Medical Research Council [MC_UU_00007/15]
- MRC [MC_UU_00007/15, MR/P008887/1, MR/N008340/1, MC_UU_12008/1, MC_PC_15075] Funding Source: UKRI
Ask authors/readers for more resources
Iterative liver injury results in progressive fibrosis disrupting hepatic architecture, regeneration potential, and liver function. Hepatic stellate cells (HSCs) are a major source of pathological matrix during fibrosis and are thought to be a functionally homogeneous population. Here, we use single-cell RNA sequencing to deconvolve the hepatic mesenchyme in healthy and fibrotic mouse liver, revealing spatial zonation of HSCs across the hepatic lobule. Furthermore, we show that HSCs partition into topographically diametric lobule regions, designated portal vein-associated HSCs (PaHSCs) and central vein-associated HSCs (CaHSCs). Importantly we uncover functional zonation, identifying CaHSCs as the dominant pathogenic collagen-producing cells in a mouse model of centrilobular fibrosis. Finally, we identify LPAR1 as a therapeutic target on collagen-producing CaHSCs, demonstrating that blockade of LPAR1 inhibits liver fibrosis in a rodent NASH model. Taken together, our work illustrates the power of single-cell transcriptomics to resolve the key collagen-producing cells driving liver fibrosis with high precision.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available