LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage.

LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage.
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DOI:
10.1016/j.celrep.2016.10.080
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发表时间:
2016-11-22
期刊:
影响因子:
8.8
通讯作者:
Mikkola HKA
Mikkola HKA
中科院分区:
生物学1区
文献类型:
--
作者:
Lee LK;Ghorbanian Y;Wang W;Wang Y;Kim YJ;Weissman IL;Inlay MA;Mikkola HKA

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发育造血的不同波和部位对胎儿和成人血液生产的贡献尚不清楚。在这里,我们确定淋巴管内皮透明质酸受体-1 (LYVE1)作为卵黄囊(YS)内皮和最终造血干细胞和祖细胞(HSPCs)的标记物。Lyve1-Cre标记妊娠中期大鼠的YS和卵黄血管内皮,但未标记背主动脉和胎盘。大多数YSHSPCs和红髓祖细胞是Lyve1-Cre谱系,但原始红细胞没有,表明它们代表不同的谱系。胎儿肝脏(FL)和成人HSPCs的Lyve1-Cre标记率为35%-40%。对循环缺陷的Ncx1−/−概念的分析发现,YS是Lyve1-Cre标记的HSPCs的主要来源。在胚胎日(E) 11.5-13.5时,FL原红细胞标记广泛,但在E16.5时减少到造血干细胞(HSC)水平,表明来自多种来源的HSC负责红细胞生成。因此,Lyve1-Cre标志着YS原始造血和最终造血的分化,并为YS最终造血和FL定植提供了一种靶向工具。Lee等人发现LYVE1是妊娠中期卵黄囊内皮和最终HSPCs中高度富集的标记物。lyve1 - cre标记的造血细胞启动胎儿肝脏红细胞生成,并产生超过三分之一的胎儿和成人造血干细胞。原始红系系由LYVE1阴性前体发育而来。
The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YSHSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages. Fetal liver (FL) and adult HSPCs showed 35%–40% Lyve1-Cre marking. Analysis of circulation-deficient Ncx1−/− concepti identified the YS as a major source of Lyve1-Cre labeled HSPCs. FL proerythroblast marking was extensive at embryonic day (E) 11.5–13.5, but decreased to hematopoietic stem cell (HSC) levels by E16.5, suggesting that HSCs from multiple sources became responsible for erythropoiesis. Lyve1-Cre thus marks the divergence between YS primitive and definitive hematopoiesis and provides a tool for targeting YS definitive hematopoiesis and FL colonization. Lee et al. identify LYVE1 as a marker that is highly enriched in yolk sac endothelium and definitive HSPCs during mid-gestation. Lyve1-Cre-labeled hematopoietic cells initiate fetal liver erythropoiesis and give rise to more than one-third of fetal and adult HSCs. The primitive erythroid lineage develops from LYVE1 negative precursors.
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