{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T17:50:17Z","timestamp":1793555417375,"version":"4.5.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"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":[[2021,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Studies of the identity and pathophysiology of fibrogenic HSCs have been hampered by a lack of genetic tools that permit specific and inducible fate\u2010mapping of these cells\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Here, by single\u2010cell RNA sequencing of nonparenchymal cells from mouse liver, we identified transcription factor 21 (\n                      <jats:italic toggle=\"yes\">Tcf21<\/jats:italic>\n                      ) as a unique marker that restricted its expression to quiescent HSCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      Tracing\n                      <jats:italic toggle=\"yes\">Tcf21<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      cells by\n                      <jats:italic toggle=\"yes\">Tcf21<\/jats:italic>\n                      \u2010CreER (Cre\u2010Estrogen Receptor fusion protein under the control of Tcf21 gene promoter) targeted ~10% of all HSCs, most of which were located at periportal and pericentral zones. These HSCs were quiescent under steady state but became activated on injuries, generating 62%\u201067% of all myofibroblasts in fibrotic livers and ~85% of all cancer\u2010associated fibroblasts (CAFs) in liver tumors. Conditional deletion of Transforming Growth Factor Beta Receptor 2 (\n                      <jats:italic toggle=\"yes\">Tgfbr2<\/jats:italic>\n                      ) by\n                      <jats:italic toggle=\"yes\">Tcf21<\/jats:italic>\n                      \u2010CreER blocked HSC activation, compromised liver fibrosis, and inhibited liver tumor progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In conclusion,\n                      <jats:italic toggle=\"yes\">Tcf21<\/jats:italic>\n                      \u2010CreER\u2013targeted perivenous stellate cells are the main source of myofibroblasts and CAFs in chronically injured livers. TGF\u2010\u03b2 signaling links HSC activation to liver fibrosis and tumorigenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.31848","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T03:51:26Z","timestamp":1617594686000},"page":"1578-1594","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":93,"title":["Perivenous Stellate Cells Are the Main Source of Myofibroblasts and Cancer\u2010Associated Fibroblasts Formed After Chronic Liver Injuries"],"prefix":"10.1097","volume":"74","author":[{"given":"Shan\u2010Shan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hepatic Oncology,Key Laboratory of Carcinogenesis and Cancer Invasion,Ministry of Education,Liver Cancer Institute, Zhongshan Hospital, Fudan University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu 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