{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:55:52Z","timestamp":1792799752496,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":76,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Fund of China","doi-asserted-by":"crossref","award":["82322011,U25A2020,82170623,82170625,82300711,82470648"],"award-info":[{"award-number":["82322011,U25A2020,82170623,82170625,82300711,82470648"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National Key R&D Program of China","award":["2023YFA1800801"],"award-info":[{"award-number":["2023YFA1800801"]}]},{"name":"the 135 projects for disciplines of excellence of West China Hospital, Sichuan University","award":["ZYYC23026,ZYGD23029"],"award-info":[{"award-number":["ZYYC23026,ZYGD23029"]}]},{"name":"the Postdoctor Research Fund of West China Hospital, Sichuan University","award":["2024HXBH049"],"award-info":[{"award-number":["2024HXBH049"]}],"id":[{"id":"https:\/\/ror.org\/011ashp19","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the International Science & Technology Cooperation Project of Sichuan","award":["2025YFHZ0120"],"award-info":[{"award-number":["2025YFHZ0120"]}]},{"name":"the Sichuan Science and Technology Program","award":["2024NSFSC0641"],"award-info":[{"award-number":["2024NSFSC0641"]}]},{"name":"the Shenzhen Medical Research Funds","award":["B2302007"],"award-info":[{"award-number":["B2302007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:p>\n                    Cellular and molecular heterogeneity in the liver has been increasingly recognized to drive liver fibrosis progression, but the particular events that occur initially in response to liver injury and trigger immune cell recruitment remain unclear. Here, we identify epigenetically aberrant liver sinusoidal endothelial cells (LSECs) as key players in this process. Mechanistically, the epigenetic readers like bromodomain-containing protein 4\u2013dependent (BRD4-dependent) super enhancers (SEs) activate proinflammatory genes, including promyelocytic leukemia (PML). The PML protein, in turn, binds BRD4 and amplifies proinflammatory angiocrine signaling through phase separation\u2013dependent SE activation via PML\/BRD4 condensate formation. In mouse models, LSEC-specific depletion of the PML\/BRD4 complex mitigates liver inflammation and fibrosis. Single-cell RNA-seq reveals that epigenetically aberrant LSECs exhibit a reprogrammed proinflammatory angiocrine landscape in mouse fibrotic livers. TIMP1\n                    <jats:sup>+<\/jats:sup>\n                    LSECs promote the recruitment of CD63\n                    <jats:sup>+<\/jats:sup>\n                    monocyte\u2013derived macrophages (MoMFs) during liver fibrosis progression. Thereby, PML\/BRD4 in LSECs governs inflammatory immune cell recruitment in liver fibrosis. Pharmacological BRD4 inhibition or epigenetic PML-SE repression alleviates liver inflammation and fibrosis. In conclusion, PML\/BRD4-mediated SE activation via phase separation drives proinflammatory angiocrine signaling in LSECs, initiating the inflammatory cascade and subsequent immune cell recruitment during liver fibrosis.\n                  <\/jats:p>","DOI":"10.1172\/jci196730","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:01:34Z","timestamp":1773763294000},"source":"Crossref","is-referenced-by-count":7,"title":["Epigenetically controlled endothelial promyelocytic leukemia drives liver inflammation and fibrosis"],"prefix":"10.1172","volume":"136","author":[{"given":"Can","family":"Gan","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enjiang","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 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