Single-Cell Transcriptomic Analysis Reveals a Hepatic Stellate Cell-Activation Roadmap and Myofibroblast Origin During Liver Fibrosis in Mice.

ABSTRACT:

Background and aims

HSCs and portal fibroblasts (PFs) are the major sources of collagen-producing myofibroblasts during liver fibrosis, depending on different etiologies. However, the mechanisms by which their dynamic gene expression directs the transition from the quiescent to the activated state-as well as their contributions to fibrotic myofibroblasts-remain unclear. Here, we analyze the activation of HSCs and PFs in CCL₄ -induced and bile duct ligation-induced fibrosis mouse models, using single-cell RNA sequencing and lineage tracing.

Approach and results

We demonstrate that HSCs, rather than PFs, undergo dramatic transcriptomic changes, with the sequential activation of inflammatory, migrative, and extracellular matrix-producing programs. The data also revea

SUBMITTER: Yang W 

PROVIDER: S-EPMC8597108 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature