{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:10:58Z","timestamp":1791443458642,"version":"4.3.3"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T00:00:00Z","timestamp":1603152000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Hepatic sinusoidal cells are known actors in the fibrogenic response to injury. Activated hepatic stellate cells (HSCs), liver sinusoidal endothelial cells, and Kupffer cells are responsible for sinusoidal capillarization and perisinusoidal matrix deposition, impairing vascular exchange and heightening the risk of advanced fibrosis. While the overall pathogenesis is well understood, functional relations between cellular transitions during fibrogenesis are only beginning to be resolved. At single\u2010cell resolution, we here explored the heterogeneity of individual cell types and dissected their transitions and crosstalk during fibrogenesis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We applied single\u2010cell transcriptomics to map the heterogeneity of sinusoid\u2010associated cells in healthy and injured livers and reconstructed the single\u2010lineage HSC trajectory from pericyte to myofibroblast. Stratifying each sinusoidal cell population by activation state, we projected shifts in sinusoidal communication upon injury. Weighted gene correlation network analysis of the HSC trajectory led to the identification of core genes whose expression proved highly predictive of advanced fibrosis in patients with nonalcoholic steatohepatitis (NASH). Among the core members of the injury\u2010repressed gene module, we identified plasmalemma vesicle\u2013associated protein (PLVAP) as a protein amply expressed by mouse and human HSCs. PLVAP expression was suppressed in activated HSCs upon injury and may hence define hitherto unknown roles for HSCs in the regulation of microcirculatory exchange and its breakdown in chronic liver disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our study offers a single\u2010cell resolved account of drug\u2010induced injury of the mammalian liver and identifies key genes that may serve important roles in sinusoidal integrity and as markers of advanced fibrosis in human NASH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31215","type":"journal-article","created":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T21:06:12Z","timestamp":1583615172000},"page":"2119-2133","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":97,"title":["Transcriptional Dynamics of Hepatic Sinusoid\u2010Associated Cells After Liver Injury"],"prefix":"10.1097","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5478-7895","authenticated-orcid":false,"given":"Mike K.","family":"Terkelsen","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology,University of Southern Denmark,Odense M,Denmark"},{"name":"Center for Functional Genomics and Tissue Plasticity (ATLAS),University of Southern Denmark,Odense M,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9510-941X","authenticated-orcid":false,"given":"Sofie M.","family":"Bendixen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology,University of Southern Denmark,Odense M,Denmark"},{"name":"Center for Functional Genomics and Tissue Plasticity (ATLAS),University of Southern Denmark,Odense M,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology,University of Southern Denmark,Odense M,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma A.H.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology,University of Southern Denmark,Odense M,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-5568","authenticated-orcid":false,"given":"Andreas F.","family":"Moeller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology,University of Southern Denmark,Odense M,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronni","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology,University of Southern Denmark,Odense M,Denmark"},{"name":"Center for Functional Genomics and Tissue Plasticity (ATLAS),University of Southern Denmark,Odense M,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0961-5787","authenticated-orcid":false,"given":"Susanne","family":"Mandrup","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology,University of Southern Denmark,Odense M,Denmark"},{"name":"Center for Functional Genomics and Tissue Plasticity (ATLAS),University of Southern Denmark,Odense M,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Schlosser","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine,University of Southern Denmark,Odense C,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-7276","authenticated-orcid":false,"given":"Thomas L.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine,University of Southern Denmark,Odense C,Denmark"},{"name":"Department of Clinical Research,University of Southern Denmark,Odense C,Denmark"},{"name":"Department of Pathology,Odense University Hospital,Odense C,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5273-1097","authenticated-orcid":false,"given":"Grith L.","family":"Sorensen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine,University of Southern Denmark,Odense C,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9598-4932","authenticated-orcid":false,"given":"Aleksander","family":"Krag","sequence":"additional","affiliation":[{"name":"Center for Functional Genomics and Tissue Plasticity (ATLAS),University of Southern Denmark,Odense M,Denmark"},{"name":"Department of Clinical Research,University of Southern Denmark,Odense C,Denmark"},{"name":"Department of Gastroenterology and Hepatology,Odense University Hospital,Odense C,Denmark"},{"name":"Department of Nephrology,Odense University Hospital,Odense C,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9264-1280","authenticated-orcid":false,"given":"Kedar N.","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology,University of Southern Denmark,Odense M,Denmark"},{"name":"Danish Institute for Advanced Study,University of Southern Denmark,Odense M,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9466-2333","authenticated-orcid":false,"given":"S\u00f6nke","family":"Detlefsen","sequence":"additional","affiliation":[{"name":"Department of Pathology,Odense University Hospital,Odense 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