中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Regulation of embryonic haematopoietic multipotency by EZH1

文献类型:期刊论文

作者Vo, Linda T. l1,2,3,4; Kinney, Melissa A.1,2,3; Barragan, Jessica1,2,3; Sousa, Patricia M.1,2,3; Jha, Deepak K.1,2,3; Han, Areum1,2,3; Cesana, Marcella1,2,3; Daley, George Q.1,2,3,4; Orkin, Stuart H.2,3,4; Liu, Xin5
刊名NATURE
出版日期2018
卷号553期号:7689页码:506-+
ISSN号0028-0836
关键词dioxin endothelial cell apoptosis EP3 p38 MAPK Bcl-2
DOI10.1038/nature25435
文献子类Article
英文摘要All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs) 1. By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation2,3. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum2,3. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin4, as well as fetal lymphoid progenitors5, develop in the yolk sac and the embryo proper, but these cells lack HSC potential. Ultimately, 'definitive' HSCs with long-term, multilineage potential and the ability to engraft irradiated adults emerge at 10.5 days post-coitum from arterial endothelium in the aorta-gonad-mesonephros and other haemogenic vasculature3. The molecular mechanisms of this reverse progression of haematopoietic ontogeny remain unexplained. We hypothesized that the definitive haematopoietic program might be actively repressed in early embryogenesis through epigenetic silencing6, and that alleviating this repression would elicit multipotency in otherwise lineage-restricted haematopoietic progenitors. Here we show that reduced expression of the Polycomb group protein EZH1 enhances multi-lymphoid output from human pluripotent stem cells. In addition, Ezh1 deficiency in mouse embryos results in precocious emergence of functional definitive HSCs in vivo. Thus, we identify EZH1 as a repressor of haematopoietic multipotency in the early mammalian embryo.
学科主题Science & Technology - Other Topics
WOS关键词PLURIPOTENT STEM-CELLS ; MOUSE EMBRYO ; DEFINED FACTORS ; BLOOD-CELLS ; CHROMATIN ; LINEAGE ; ENDOTHELIUM ; PROGENITORS ; RESISTANCE ; LEUKEMIA
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000423971100041
版本出版稿
源URL[http://202.127.25.144/handle/331004/1025]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA;
2.Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA;
3.Dana Farber Canc Inst, Boston, MA 02115 USA;
4.Harvard Med Sch, Boston, MA 02115 USA;
5.Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Childrens Med Ctr, Res Inst, Dallas, TX USA;
6.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai, Peoples R China;
7.Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA;
8.Howard Hughes Med Inst, Boston, MA 02115 USA;
9.Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA,
推荐引用方式
GB/T 7714
Vo, Linda T. l,Kinney, Melissa A.,Barragan, Jessica,et al. Regulation of embryonic haematopoietic multipotency by EZH1[J]. NATURE,2018,553(7689):506-+.
APA Vo, Linda T. l.,Kinney, Melissa A..,Barragan, Jessica.,Sousa, Patricia M..,Jha, Deepak K..,...&,.(2018).Regulation of embryonic haematopoietic multipotency by EZH1.NATURE,553(7689),506-+.
MLA Vo, Linda T. l,et al."Regulation of embryonic haematopoietic multipotency by EZH1".NATURE 553.7689(2018):506-+.

入库方式: OAI收割

来源:上海营养与健康研究所

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