{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:39:26Z","timestamp":1785425966035,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,17]]},"group-title":"Pathology","reference-count":40,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["2R01DK080789-12A1"],"award-info":[{"award-number":["2R01DK080789-12A1"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012025","name":"New York University Abu Dhabi","doi-asserted-by":"crossref","award":["AD188"],"award-info":[{"award-number":["AD188"]}],"id":[{"id":"10.13039\/100012025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012025","name":"New York University Abu Dhabi","doi-asserted-by":"crossref","award":["CGSB13"],"award-info":[{"award-number":["CGSB13"]}],"id":[{"id":"10.13039\/100012025","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Regeneration depends on tightly coordinated transcriptional programs governed by a dynamic epigenetic landscape to regulate cell identity, proliferation, and tissue remodelling following injury. The liver is highly regenerative due to its ability to rapidly upregulate genes that drive the cell cycle and other genes important for hepatocyte proliferation. In the uninjured liver, many of these genes are poised for activation based on promoter occupancy of trimethylated histone 3 lysine 27 (H3K27me3) and regenerative stimulus provided by partial hepatectomy leads to evacuation of this mark, suggesting this is a key component of proregenerative gene regulation in the liver. H3K27me3 is deposited by the polycomb repressive complex 2 (PRC2). Were we deplete H3K27me3 using hepatocyte specific deletion of key component of PRC2, Embryonic Ectoderm Development\n                  <jats:italic>\n                    (Eed\n                    <jats:sup>HepKO<\/jats:sup>\n                  <\/jats:italic>\n                  ). This results in reduced liver size, increased hepatocyte death, proliferation, and fibrosis associated with upregulation of cell cycle and fibrogenic genes. Though these mice are less likely to survive two-thirds partial hepatectomy than WT (WT) controls, those that do survive increase liver mass faster than WTs. Importantly, genes occupied by H3K27me3 in uninjured WT livers are upregulated in EED\n                  <jats:sup>HepKO<\/jats:sup>\n                  livers, and become further induced following PH. This demonstrates that PRC2 loss induces liver injury and dysregulates pro-regenerative gene expression, highlighting that epigenetic modulation depends requires precise targeting to achieve enhanced regenerative\n                <\/jats:p>","DOI":"10.64898\/2026.03.13.711572","type":"posted-content","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:03:59Z","timestamp":1773763439000},"source":"Crossref","is-referenced-by-count":0,"title":["Hepatocyte Embryonic Ectoderm Development (Eed) Deficiency Causes Liver Injury, Fibrosis, and Impacts Liver Regeneration"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1734-6505","authenticated-orcid":false,"given":"Yousra","family":"Ajouaou","sequence":"first","affiliation":[{"name":"Program in Biology, NYU Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates"},{"name":"Center for Genomics and Systems Biology, NYU Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Griffin","sequence":"additional","affiliation":[{"name":"Program in Biology, NYU Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sade","family":"Chaffatt","sequence":"additional","affiliation":[{"name":"Program in Biology, NYU Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7865-9251","authenticated-orcid":false,"given":"Charlene","family":"Chen","sequence":"additional","affiliation":[{"name":"Program in Biology, NYU Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balnur","family":"Ibrash","sequence":"additional","affiliation":[{"name":"Program in Biology, NYU Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7603-3210","authenticated-orcid":false,"given":"Martine","family":"McManus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1100-4125","authenticated-orcid":false,"given":"Kirsten C.","family":"Sadler","sequence":"additional","affiliation":[{"name":"Program in Biology, NYU Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates"},{"name":"Center for Genomics and Systems Biology, NYU Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070604551012000_2026.03.13.711572v3.1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s00018-024-05206-2","article-title":"Epigenomic insights into common human disease pathology","volume":"81","year":"2024","journal-title":"Cell Mol Life Sci"},{"key":"2026070604551012000_2026.03.13.711572v3.2","doi-asserted-by":"crossref","unstructured":"Griazeva ED , Fedoseeva DM , Radion EI , Ershov PV , Meshkov IO , Semyanihina AV , Makarova AS , et al. 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