{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:00:10Z","timestamp":1791061210189,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/ http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims:<\/jats:title>\n            <jats:p>Relative roles of HSCs and portal fibroblasts in alcoholic hepatitis (AH) are unknown. We aimed to identify subpopulations of collagen type 1 alpha 1 (Col1a1)\u2013expressing cells in a mouse AH model by single\u2010cell RNA sequencing (scRNA\u2010seq) and filtering the cells with the HSC (lecithin retinol acyltransferase [Lrat]) and portal fibroblast (Thy\u20101 cell surface antigen [Thy1] and fibulin 2 [Fbln2]) markers and vitamin A (VitA) storage.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>Col1a1\u2013green fluorescent protein (GFP) mice underwent AH, CCl<jats:sub>4<\/jats:sub>, and bile duct ligation (BDL) procedures to have comparable F1\u2010F2 liver fibrosis. Col1a1\u2010expressing cells were sorted via FACS by VitA autofluorescence and GFP for single\u2010cell RNA sequencing. In AH, approximately 80% of Lrat+Thy1\u2212Fbln2\u2212 activated HSCs were VitA\u2010depleted (vs. ~13% in BDL and CCl<jats:sub>4<\/jats:sub>). Supervised clustering identified a subset co\u2010expressing Lrat and Fbln2 (Lrat+Fbln2+), which expanded 44\u2010fold, 17\u2010fold, and 1.3\u2010fold in AH, BDL, and CCl<jats:sub>4<\/jats:sub>. Lrat+Fbln2+ cells had 3\u201315\u2010times inductions of profibrotic, myofibroblastic, and immunoregulatory genes versus Lrat+Fbln2\u2212 cells, but 2\u20134\u2010times repressed HSC\u2010selective genes. AH activated HSCs had up\u2010regulated inflammatory (chemokine [C\u2010X\u2010C motif] ligand 2 [Cxcl2], chemokine [C\u2010C motif] ligand 2), antimicrobial (Il\u201033, Zc3h12a), and antigen presentation (H2\u2010Q6, H2\u2010T23) genes versus BDL and CCl<jats:sub>4<\/jats:sub>. Computational deconvolution of AH versus normal human bulk\u2010liver RNA\u2010sequencing data supported an expansion of LRAT+FBLN2+ cells in AH; AH patient liver immunohistochemistry showed FBLN2 staining along fibrotic septa enriched with LRAT+ cells; and <jats:italic toggle=\"yes\">in situ<\/jats:italic> hybridization confirmed co\u2010expression of FBLN2 with CXCL2 and\/or human leukocyte antigen E in patient AH. Finally, HSC tracing in Lrat\u2010Cre;Rosa26mTmG mice detected GFP+FBLN2+ cells in AH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32793","type":"journal-article","created":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T13:49:26Z","timestamp":1664632166000},"page":"212-224","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":14,"title":["Emergence of highly profibrotic and proinflammatory Lrat + Fbln2 + HSC subpopulation in alcoholic hepatitis"],"prefix":"10.1097","volume":"78","author":[{"given":"Steven","family":"Balog","sequence":"first","affiliation":[{"name":"Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reika","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA"},{"name":"University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Q.","family":"Pan","sequence":"additional","affiliation":[{"name":"Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khairat B.","family":"El\u2010Baradie","sequence":"additional","affiliation":[{"name":"Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Yeon","family":"Choi","sequence":"additional","affiliation":[{"name":"Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Sinha","sequence":"additional","affiliation":[{"name":"Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihong","family":"Yang","sequence":"additional","affiliation":[{"name":"Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0398-8395","authenticated-orcid":false,"given":"Kinji","family":"Asahina","sequence":"additional","affiliation":[{"name":"Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA"},{"name":"Central Research Laboratory, Shiga University of Medical Sciences, Seta Tsukinowa\u2010cho Otsu, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibu","family":"Chen","sequence":"additional","affiliation":[{"name":"USC Libraries Bioinformatic Services of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"USC Libraries Bioinformatic Services of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Salomon","sequence":"additional","affiliation":[{"name":"Department Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley W.\u2010K.","family":"Ng","sequence":"additional","affiliation":[{"name":"Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Southern California Research Center for ALPD and Cirrhosis, 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