{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T18:49:43Z","timestamp":1794422983464,"version":"4.9.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"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":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      In clinical and experimental NASH, the origin of the scar\u2010forming myofibroblast is the HSC. We used\n                      <jats:italic toggle=\"yes\">foz\/foz<\/jats:italic>\n                      mice on a Western diet to characterize in detail the phenotypic changes of HSCs in a NASH model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      We examined the single\u2010cell expression profiles (scRNA sequencing) of HSCs purified from the normal livers of\n                      <jats:italic toggle=\"yes\">foz\/foz<\/jats:italic>\n                      mice on a chow diet, in NASH with fibrosis of\n                      <jats:italic toggle=\"yes\">foz\/foz<\/jats:italic>\n                      mice on a Western diet, and in livers during regression of NASH after switching back to a chow diet. Selected genes were analyzed using immunohistochemistry, quantitative real\u2010time PCR, and short hairpin RNA knockdown in primary mouse HSCs. Our analysis of the normal liver identified two distinct clusters of quiescent HSCs that correspond to their acinar position of either pericentral vein or periportal vein. The NASH livers had four distinct HSC clusters, including one representing the classic fibrogenic myofibroblast. The three other HSC clusters consisted of a proliferating cluster, an intermediate activated cluster, and an immune and inflammatory cluster. The livers with NASH regression had one cluster of inactivated HSCs, which was similar to, but distinct from, the quiescent HSCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Analysis of single\u2010cell RNA sequencing in combination with an interrogation of previous studies revealed an unanticipated heterogeneity of HSC phenotypes under normal and injured states.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.31743","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T08:07:56Z","timestamp":1612685276000},"page":"667-685","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":152,"title":["Heterogeneity of HSCs in a Mouse Model of NASH"],"prefix":"10.1097","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6548-9658","authenticated-orcid":false,"given":"Sara Brin","family":"Rosenthal","sequence":"first","affiliation":[{"name":"Center for Computational Biology and Bioinformatics,University of California, San Diego,La Jolla,CA"},{"name":"Department of Medicine,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of California, San Diego,La Jolla,CA"},{"name":"Department of Surgery,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souradipta","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debanjan","family":"Dhar","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina P.","family":"Pasillas","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Ricciardelli","sequence":"additional","affiliation":[{"name":"Institute for Genomic Medicine,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick Z.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ty D.","family":"Troutman","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Kisseleva","sequence":"additional","affiliation":[{"name":"Department of Surgery,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K.","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of California, San Diego,La Jolla,CA"},{"name":"Department of Cellular and Molecular Medicine,University of California, San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of California, San Diego,La 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