{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:58:56Z","timestamp":1788479936927,"version":"build-2803163510"},"reference-count":70,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-NIDDK","award":["DK102456,DK136177"],"award-info":[{"award-number":["DK102456,DK136177"]}]},{"name":"AHA","award":["Career Development Award"],"award-info":[{"award-number":["Career Development Award"]}]},{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"crossref","award":["Rackham Predoctoral Fellowship"],"award-info":[{"award-number":["Rackham Predoctoral Fellowship"]}],"id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Michigan Advanced Genomics Core and NCI","award":["P30CA046592"],"award-info":[{"award-number":["P30CA046592"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>\n                    Hepatocyte senescence is increasingly recognized as a pathogenic driver of metabolic dysfunction\u2013associated steatohepatitis (MASH). Through single-nucleus transcriptomic profiling, we identified a discrete population of disease-associated hepatocytes (daHep) exhibiting enrichment for senescence markers in MASH livers. The emergence of senescent hepatocytes was associated with a marked induction of hepatic thymocyte selection associated (THEMIS) expression in both murine and human MASH. Genetic ablation of\n                    <jats:italic>Themis<\/jats:italic>\n                    , either globally or specifically in hepatocytes, resulted in significant expansion of daHep and senescent hepatocyte populations and exacerbated MASH pathology in mice. Single-nucleus transcriptomic analysis revealed a central role for THEMIS in shaping the cellular landscape of both parenchymal and nonparenchymal compartments within the MASH liver microenvironment. Conversely, adeno-associated virus\u2013mediated overexpression of THEMIS suppressed hepatocyte senescence and attenuated diet-induced MASH. Mechanistic studies revealed that THEMIS deficiency promoted aberrant ERK phosphorylation and hepatocyte senescence. These findings establish THEMIS as a critical hepatoprotective factor that restrains hepatocyte senescence and mitigates metabolic liver disease progression.\n                  <\/jats:p>","DOI":"10.1172\/jci199303","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:00:58Z","timestamp":1777572058000},"source":"Crossref","is-referenced-by-count":1,"title":["THEMIS attenuates MASH by suppressing disease-associated hepatocyte induction and hepatocyte senescence in mice"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1015-9993","authenticated-orcid":true,"given":"Xiaoxue","family":"Qiu","sequence":"first","affiliation":[{"name":"Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Lu","sequence":"additional","affiliation":[{"name":"Life Sciences 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