Depletion of polycomb repressive complex 2 core component EED impairs fetal hematopoiesis.
Depletion of polycomb repressive complex 2 core component EED impairs fetal hematopoiesis.
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多梳抑制复合物 2 核心成分 EED 的耗竭会损害胎儿造血功能
DOI：
10.1038/cddis.2017.163
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发表时间：
2017-04-13
影响因子：
9
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Yu W;Zhang F;Wang S;Fu Y;Chen J;Liang X;Le H;Pu WT;Zhang B
多梳阻遏复合物2（Polycomb repressive complex 2，PRC 2）是一种H3 K27 me 3甲基转移酶复合物，通过抑制异位转录程序来促进多种器官的发育。然而，目前对PRC 2在血液和血管发育中的作用知之甚少。在这项研究中，我们询问的功能胚胎外胚层发育（EED），核心PRC 2组件，在内皮和造血组织失活floxed小鼠EED等位基因与Tie 2Cre，催化重组内皮和造血谱系。小鼠EED fl/fl; Tie 2Cre（EED CKO）胚胎在胚胎第（E）13.5天死亡。我们没有观察到血管或心脏瓣膜的结构异常，这表明EED在血管发育的初始步骤中被包裹在内皮细胞中。EED CKO胚胎苍白，肝脏异常。胎肝细胞的流式细胞术显示，EED耗竭显着阻碍红系成熟。髓系祖细胞和粒细胞和巨噬细胞相应增加，表明髓系分化途径减弱。此外，EED耗竭损害造血干细胞的生成。总的来说，我们的研究表明，在Tie 2Cre重组胚胎细胞内，EED是适当的红细胞生成和造血祖细胞和干细胞形成所需的，但对于内皮谱系定型和早期血管形成是必需的。
Polycomb repressive complex 2 (PRC2), a H3K27me3 methyltransferase complex, promotes the development of many organs by silencing ectopic transcription program. However, currently little is known about the role of PRC2 in blood and vascular development. In this study, we interrogated the function of embryonic ectoderm development (EED), a core PRC2 component, in both endothelial and hematopoietic tissues by inactivating a floxed murine EED allele with Tie2Cre, which catalyzes recombination in endothelial and hematopoietic lineages. Murine EED fl/fl; Tie2Cre (EED CKO) embryos died at embryonic day (E) 13.5. We did not observe structural abnormalities of blood vessels or cardiac valves, suggesting that EED is dispensable in endothelial cells for initial steps of vascular development. EED CKO embryos were pale and had abnormal livers. Flow cytometry of fetal liver cells showed that EED depletion significantly impeded erythroid maturation. There was a corresponding increase in myeloid progenitors and granulocytes and macrophages, suggesting an attenuated differentiation path in myeloid lineages. Moreover, EED depletion impaired the generation of hematopoietic stem cells. Collectively, our study demonstrates that within Tie2Cre-recombined embryonic cells, EED is required for proper erythropoiesis and for formation of hematopoietic progenitor and stem cells, but is dispensable for endothelial lineage commitment and early vascular patterning.