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HSC are sinusoidal pericytes that act as myofibroblast precursors after liver injury. Single cell RNA sequencing approaches have recently helped to differentiate central and portal HSC. A specific Cre line to lineage trace portal HSC has not yet been described. We used three Cre lines (Lrat-Cre, PDGFR\u03b2-CreER<jats:sup>T2<\/jats:sup> and SMMHC-CreER<jats:sup>T2<\/jats:sup>) known to label mesenchymal cells including HSC in combination with a tdTomato-expressing reporter. All three Cre lines labeled populations of HSC as well as smooth muscle cells (SMC). Using the SMMHC-CreER<jats:sup>T2<\/jats:sup>, we identified a subtype of HSC in the periportal area of the hepatic lobule (termed zone 1-HSC). We lineage traced tdTomato-expressing zone 1-HSC over 1\u00a0year, described fibrotic behavior in two fibrosis models and investigated their possible role during fibrosis. This HSC subtype resides in zone 1 under healthy conditions; however, zonation is disrupted in preclinical models of liver fibrosis (CCl<jats:sub>4<\/jats:sub> and MASH). Zone 1-HSC do not transform into \u03b1SMA-expressing myofibroblasts. Rather, they participate in sinusoidal capillarization. We describe a novel subtype of HSC restricted to zone 1 under physiological conditions and its possible function after liver injury. In contrast to the accepted notion, this HSC subtype does not transform into \u03b1SMA-positive myofibroblasts; rather, zone 1-HSC adopt properties of capillary pericytes, thereby participating in sinusoidal capillarization.<\/jats:p>","DOI":"10.1038\/s41598-024-69898-z","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T20:18:11Z","timestamp":1723580291000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hepatic stellate cells in zone 1 engage in capillarization rather than myofibroblast formation in murine liver fibrosis"],"prefix":"10.1038","volume":"14","author":[{"given":"Muhammad Ashfaq","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Harrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Schwiering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Groneberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Friebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"69898_CR1","doi-asserted-by":"publisher","first-page":"5503","DOI":"10.1172\/JCI74119","volume":"124","author":"C Kordes","year":"2014","unstructured":"Kordes, C., Sawitza, I., Gotze, S., Herebian, D. & Haussinger, D. 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