{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:26:48Z","timestamp":1791462408609,"version":"4.3.4"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Liver fibrosis and cirrhosis have limited therapeutic options and represent a serious unmet patient need. Recent use of single\u2010cell RNA sequencing (scRNAseq) has identified enriched cell types infiltrating cirrhotic livers but without defining the microanatomical location of these lineages thoroughly. To assess whether fibrotic liver regions specifically harbor enriched cell types, we explored whether whole\u2010tissue spatial transcriptomics combined with scRNAseq and gene deconvolution analysis could be used to localize cell types in cirrhotic explants of patients with end\u2010stage liver disease (total <jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a08; primary sclerosing cholangitis, <jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a04; primary biliary cholangitis, <jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a02, alcohol\u2010related liver disease, <jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a02). Spatial transcriptomics clearly identified tissue areas of distinct gene expression that strongly correlated with the total area (Spearman <jats:italic toggle=\"yes\">r<\/jats:italic>\u00a0=\u00a00.97, <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0=\u00a00.0004) and precise location (parenchyma, 87.9% mean congruency; range, 73.1%\u201397.1%; fibrosis, 68.5% mean congruency; range, 41.0%\u201391.7%) of liver regions classified as parenchymal or fibrotic by conventional histology. Deconvolution and enumeration of parenchymal and fibrotic gene content as measured by spatial transcriptomics into distinct cell states revealed significantly higher frequencies of <jats:italic toggle=\"yes\">ACTA2<\/jats:italic>+ <jats:italic toggle=\"yes\">FABP4<\/jats:italic>+ and <jats:italic toggle=\"yes\">COL3A1<\/jats:italic>+ mesenchymal cells, <jats:italic toggle=\"yes\">IL17RA<\/jats:italic>+ <jats:italic toggle=\"yes\">S100A8<\/jats:italic>+ and <jats:italic toggle=\"yes\">FCER1G<\/jats:italic>+ tissue monocytes, <jats:italic toggle=\"yes\">VCAM1<\/jats:italic>+ <jats:italic toggle=\"yes\">SDC3<\/jats:italic>+ Kupffer cells, <jats:italic toggle=\"yes\">CCL4<\/jats:italic>+ <jats:italic toggle=\"yes\">CCL5<\/jats:italic>+ <jats:italic toggle=\"yes\">KLRB1<\/jats:italic>+ and <jats:italic toggle=\"yes\">GZMA<\/jats:italic>+ <jats:italic toggle=\"yes\">IL17RA<\/jats:italic>+ T cells and <jats:italic toggle=\"yes\">HLA\u2010DR<\/jats:italic>+, <jats:italic toggle=\"yes\">CD37<\/jats:italic>+ <jats:italic toggle=\"yes\">CXCR4<\/jats:italic>+ and <jats:italic toggle=\"yes\">IGHM<\/jats:italic>+ <jats:italic toggle=\"yes\">IGHG<\/jats:italic>+ B cells in fibrotic liver regions compared with parenchymal areas of cirrhotic explants. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Our findings indicate that spatial transcriptomes of parenchymal and fibrotic liver regions express unique gene content within cirrhotic liver and demonstrate proof of concept that spatial transcriptomes combined with additional RNA sequencing methodologies can refine the localization of gene content and cell lineages in the search for antifibrotic targets.<\/jats:p>","DOI":"10.1002\/hep4.2001","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T05:58:16Z","timestamp":1655791096000},"page":"2538-2550","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":84,"title":["Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis"],"prefix":"10.1097","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9523-7515","authenticated-orcid":false,"given":"Brian K.","family":"Chung","sequence":"first","affiliation":[{"name":"Norwegian PSC Research Center,Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine,Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"Institute of Clinical Medicine, Faculty of Medicine,University of Oslo,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"\u00d8gaard","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center,Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine,Oslo University Hospital, Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik Mikael","family":"Reims","sequence":"additional","affiliation":[{"name":"Department of Pathology,Oslo University Hospital, Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H.","family":"Karlsen","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center,Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine,Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"Institute of Clinical Medicine, Faculty of Medicine,University of Oslo,Oslo,Norway"},{"name":"Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation,Oslo University Hospital, Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6903-6878","authenticated-orcid":false,"given":"Espen","family":"Melum","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center,Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine,Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"Institute of Clinical Medicine, Faculty of Medicine,University of Oslo,Oslo,Norway"},{"name":"Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation,Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"Hybrid Technology Hub\u2010Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine,University of Oslo,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"key":"hep42001-bib-0001-20241118","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/S0140-6736(18)32203-7","article-title":"Global, regional, and national age\u2010sex\u2010specific mortality for 282 causes of death in 195 countries and territories, 1980\u20132017: a systematic analysis for the global burden of disease study 2017","volume":"392","year":"2018","journal-title":"Lancet"},{"key":"hep42001-bib-0002-20241118","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.bpg.2011.02.001","article-title":"Fibrosis in autoimmune and cholestatic Liver disease","volume":"25","year":"2011","journal-title":"Best Pract Res Clin 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