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BACKGROUND AND AIMS Relative roles of hepatic stellate cells (HSCs) and portal fibroblasts (PFs) in alcoholic hepatitis (AH) are unknown. We aimed to identify subpopulations of Col1a1- expressing cells in a mouse AH model by single cell RNA sequencing (scRNA-seq) and filtering the cells with the HSC (Lrat) and PF (Thy1, Fbln2) markers and vitamin A (VitA) storage. APPROACH AND RESULTS Col1a1-GFP mice underwent AH, CCl4 and BDL procedures to have comparable F1-2 liver fibrosis. Col1a1-expressing cells were sorted via FACS by VitA autofluorescence and GFP for scRNA-seq. In AH, ~80% of Lrat+ Thy1- Fbln2- activated HSCs (aHSCs) were VitA-depleted vs. ~13% in BDL and CCl4. Supervised clustering identified a novel subset co-expressing Lrat and Fbln2 (Lrat+ Fbln2+ ), which expanded 44, 17, and 1.3-fold in AH, BDL, and CCl4. Lrat+ Fbln2+ cells had 3-15x inductions of profibrotic, myofibroblastic and immunoregulatory genes vs. Lrat+ Fbln2- cells but 2-4x repressed HSC-selective genes. AH aHSC had upregulated inflammatory (Cxcl2, Ccl2), antimicrobial (Il33, Zc3h12a) and antigen presentation (H2-Q6, H2-T23) genes vs. BDL and CCl4. Computational deconvolution of AH vs. normal human bulk liver RNA-seq data supported an expansion of LRAT+ FBLN2+ cells in AH; AH patient liver IHC showed FBLN2 staining along fibrotic septa enriched with LRAT+ cells; and in-situ hybridization confirmed co-expression of FBLN2 with CXCL2 and/or HLA-E in patient AH. Finally, HSC tracing in Lrat-Cre;Rosa26mTmG mice, detected GFP+ FBLN2+ cells in AH. CONCLUSION A highly profibrotic, inflammatory, and immunoregulatory Lrat+ Fbln2+ subpopulation emerges from HSCs in AH and may contribute to the inflammatory and immunoreactive nature of AH.