Recent advancements in single-cell transcriptomics have uncovered the significant heterogeneity of hepatic stellate cells (HSCs), highlighting the unique gene expression profiles and functions of different HSC subpopulations. At the 2024 American Association for the Study of Liver Diseases (AASLD) Annual Meeting, Dr. Hong You and Dr. Aiting Yang from Beijing Friendship Hospital, Capital Medical University, presented their groundbreaking study, which identified a high-expression ECM1 (extracellular matrix protein 1) HSC subpopulation as a pivotal player in fibrosis regression. Their work was honored with the "Outstanding Poster Presentation" award, offering new insights into the pathogenesis of liver fibrosis and guiding the development of novel antifibrotic therapies.
Research aimed to pinpoint HSC subpopulations vital for liver fibrosis regression. Two mouse models, induced by carbon tetrachloride (CCl₄) and choline-deficient, L-amino acid-supplemented (CDAA) diets, were used. HSC proliferation was inhibited or Lrat-positive HSCs were ablated. RNA sequencing (RNA-seq) identified novel HSC subpopulations. Key findings include: blocking HSC proliferation with PdgfraΔHSC mice halted CCl₄-induced fibrosis but worsened CDAA-induced NASH fibrosis; ablating Lrat+ HSCs inhibited CCl₄-induced fibrosis but aggravated CDAA-induced fibrosis, hinting at a protective HSC subpopulation in the CDAA model. RNA-seq revealed a novel antifibrotic HSC subpopulation, ECM1⁺ HSCs. Transgenic mice with HSC-specific Ecm1 overexpression showed significant fibrosis reduction, decreased liver inflammation, and blocked fibrosis progression in the CCl₄ model. Thus, ECM1⁺ HSCs are crucial for fibrosis regression, and targeting ECM1 in HSCs offers promising antifibrotic therapy approaches.
