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The WD-repeat protein embryonic ectoderm development (EED) is a non-catalytic but an essential component of PRC2 and its mutations were identified in hematopoietic malignancies. To clarify the role(s) of EED in adult hematopoiesis and leukemogenesis, we generated <jats:italic>Eed<\/jats:italic> conditional knockout (<jats:italic>Eed<\/jats:italic><jats:sup>\u0394\/\u0394<\/jats:sup>) mice. <jats:italic>Eed<\/jats:italic><jats:sup>\u0394\/\u0394<\/jats:sup> mice died in a short period with rapid decrease of hematopoietic cells. Hematopoietic stem\/progenitor cells (HSPCs) were markedly decreased with impaired bone marrow (BM) repopulation ability. Cell cycle analysis of HSPCs demonstrated increased S-phase fraction coupled with suppressed G0\/G1 entry. Genes encoding cell adhesion molecules are significantly enriched in <jats:italic>Eed<\/jats:italic><jats:sup>\u0394\/\u0394<\/jats:sup> HSPCs and consistently, <jats:italic>Eed<\/jats:italic><jats:sup>\u0394\/\u0394<\/jats:sup> HSPCs exhibited increased attachment to a major extracellular matrix component, fibronectin. Thus, EED deficiency increases proliferation on one side but promotes quiescence possibly by enhanced adhesion to the hematopoietic niche on the other and these conflicting events would lead to abnormal differentiation and functional defect of <jats:italic>Eed<\/jats:italic><jats:sup>\u0394\/\u0394<\/jats:sup> HSPCs. In addition, <jats:italic>Eed<\/jats:italic> haploinsufficiency induced hematopoietic dysplasia and <jats:italic>Eed<\/jats:italic> heterozygous mice were susceptible to malignant transformation and developed leukemia in cooperation with <jats:italic>Evi1<\/jats:italic> overexpression. Our results demonstrated differentiation stage-specific and dose-dependent roles of EED in normal hematopoiesis and leukemogenesis.<\/jats:p>","DOI":"10.1038\/srep29454","type":"journal-article","created":{"date-parts":[[2016,7,19]],"date-time":"2016-07-19T09:14:51Z","timestamp":1468919691000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Maintenance of the functional integrity of mouse hematopoiesis by EED and promotion of leukemogenesis by EED haploinsufficiency"],"prefix":"10.1038","volume":"6","author":[{"given":"Kenichiro","family":"Ikeda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norimasa","family":"Yamasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Nakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Sera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Nagamachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Miyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiyo","family":"Takubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Kanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Oda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Wolff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zen-ichiro","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Ichinohe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Suda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Inaba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,19]]},"reference":[{"key":"BFsrep29454_CR1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/83730","volume":"27","author":"L Jackson-Grusby","year":"2001","unstructured":"Jackson-Grusby, L. et al. 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