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Single-cell fixed RNAseq of liver fibrosis progression and regression

ABSTRACT: Liver fibrosis regression is a dynamic process involving a variety of hepatic and immune cell populations. Using single-cell fixed RNA profiling (FLEX) on mouse livers from control, TAA-induced cirrhotic, and regression phases, we analyzed 38,136 cells across 10 major cell types. Regression was characterized by the emergence of pericentral hepatocytes enriched in detoxification and antioxidant genes (e.g., Cyp2e1, Txn1), which secreted RARRES2 to modulate hepatic stellate cells (HSCs). Recovered liver sinusoidal endothelial cells (LSECs) expressed scar-resolving genes (Mmp14, Ctsl) and restored fenestrae structure. Kupffer cells regained anti-inflammatory phenotypes, while SEMA4D, produced by monocyte-derived macrophages, activated HSCs; blockade of SEMA4D reduced fibrosis in vivo. Fibrogenic cholangiocyte subsets and LMCD1⁺ HSCs were diminished during regression, with LMCD1 identified as a novel marker of HSC activation. Additionally, NK/T cells, B cells, and neutrophils displayed recovery-associated transcriptional signatures. This single-cell atlas uncovers key transcriptional programs and intercellular interactions driving fibrosis resolution and highlights potential therapeutic targets for chronic liver disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE295293 | GEO | 2026/03/27

REPOSITORIES: GEO

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