{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:09:21Z","timestamp":1791493761176,"version":"4.3.4"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>In liver fibrosis, myofibroblasts derive from HSCs and as yet undefined mesenchymal cells. We aimed to identify portal mesenchymal progenitors of myofibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      Portal mesenchymal cells were isolated from mouse bilio\u2010vascular tree and analyzed by single\u2010cell RNA\u2010sequencing. Thereby, we uncovered the landscape of portal mesenchymal cells in homeostatic mouse liver. Trajectory analysis enabled inferring a small cell population further defined by surface markers used to isolate it. This population consisted of portal fibroblasts with mesenchymal stem cell features (PMSCs), i.e., high clonogenicity and trilineage differentiation potential, that generated proliferative myofibroblasts, contrasting with nonproliferative HSC\u2010derived myofibroblasts (\u2010MF). Using bulk RNA\u2010sequencing, we built oligogene signatures of the two cell populations that remained discriminant across myofibroblastic differentiation.\n                      <jats:italic toggle=\"yes\">SLIT2<\/jats:italic>\n                      , a prototypical gene of PMSC\/PMSC\u2010MF signature, mediated profibrotic and angiogenic effects of these cells, which conditioned medium promoted HSC survival and endothelial cell tubulogenesis. Using PMSC\/PMSC\u2010MF 7\u2010gene signature and slit guidance ligand 2 fluorescent in situ hybridization, we showed that PMSCs display a perivascular portal distribution in homeostatic liver and largely expand with fibrosis progression, contributing to the myofibroblast populations that form fibrotic septa, preferentially along neovessels, in murine and human liver disorders, irrespective of etiology. We also unraveled a 6\u2010gene expression signature of HSCs\/HSC\u2010MFs that did not vary in these disorders, consistent with their low proliferation rate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PMSCs form a small reservoir of expansive myofibroblasts, which, in interaction with neovessels and HSC\u2010MFs that mainly arise through differentiation from a preexisting pool, underlie the formation of fibrotic septa in all types of liver diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.32456","type":"journal-article","created":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T10:55:41Z","timestamp":1647082541000},"page":"1360-1375","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":91,"title":["Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis"],"prefix":"10.1097","volume":"76","author":[{"given":"Lin","family":"Lei","sequence":"first","affiliation":[{"name":"Centre de Recherche Saint\u2010Antoine (CRSA),Institute of Cardiometabolism and Nutrition (ICAN),Sorbonne Universit\u00e9,INSERM,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix","family":"Bruneau","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology,Charit\u00e9 University Medicine Berlin,Berlin,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haquima","family":"El Mourabit","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint\u2010Antoine (CRSA),Institute of Cardiometabolism and Nutrition (ICAN),Sorbonne Universit\u00e9,INSERM,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Gu\u00e9gan","sequence":"additional","affiliation":[{"name":"Institut du Cerveau (ICM),Bioinformatics\/Biostatistics iCONICS Facility,Sorbonne Universit\u00e9,INSERM,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"Folseraas","sequence":"additional","affiliation":[{"name":"Division of Surgery,Inflammatory Medicine and Transplantation,Research Institute of Internal Medicine,Oslo University Hospital Rikshospitalet,Norwegian PSC Research Center,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lemoinne","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint\u2010Antoine (CRSA),Institute of Cardiometabolism and Nutrition (ICAN),Sorbonne Universit\u00e9,INSERM,Paris,France"},{"name":"Department of Hepatology,Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (CRMR MIVB\u2010H, ERN RARE\u2010LIVER),Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP),Saint\u2010Antoine Hospital,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom Hemming","family":"Karlsen","sequence":"additional","affiliation":[{"name":"Division of Surgery,Inflammatory Medicine and Transplantation,Research Institute of Internal Medicine,Oslo University Hospital Rikshospitalet,Norwegian PSC Research Center,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Hoareau","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9,INSERM,UMS Production et Analyse de Donn\u00e9es en Sciences de la Vie et en Sant\u00e9 (PASS),Cytom\u00e9trie Piti\u00e9\u2010Salp\u00eatri\u00e8re (CyPS),Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Morichon","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint\u2010Antoine (CRSA),Institute of Cardiometabolism and Nutrition (ICAN),Sorbonne Universit\u00e9,INSERM,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Gonzalez\u2010Sanchez","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint\u2010Antoine (CRSA),Institute of Cardiometabolism and Nutrition (ICAN),Sorbonne Universit\u00e9,INSERM,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Goumard","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint\u2010Antoine (CRSA),Institute of Cardiometabolism and Nutrition (ICAN),Sorbonne Universit\u00e9,INSERM,Paris,France"},{"name":"Departments of Hepatology,Hepatobiliary Surgery and Liver Transplantation,AP\u2010HP,Sorbonne Universit\u00e9,ICAN,Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6865-3791","authenticated-orcid":false,"given":"Vlad","family":"Ratziu","sequence":"additional","affiliation":[{"name":"Departments of Hepatology,Hepatobiliary Surgery and Liver Transplantation,AP\u2010HP,Sorbonne Universit\u00e9,ICAN,Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Charbord","sequence":"additional","affiliation":[{"name":"Institut de Biologie Paris Seine (IBPS),Laboratoire de Biologie du D\u00e9veloppement,Sorbonne Universit\u00e9,CNRS,INSERM,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Gautheron","sequence":"additional","affiliation":[{"name":"Centre de Recherche Saint\u2010Antoine (CRSA),Institute of Cardiometabolism and Nutrition (ICAN),Sorbonne 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