Endomucin, a CD34-like sialomucin, marks hematopoietic stem cells throughout development.
Endomucin, a CD34-like sialomucin, marks hematopoietic stem cells throughout development.
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内素蛋白是一种CD34样唾液素，在整个发育过程中都标志着造血干细胞。
DOI：
10.1084/jem.20051325
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发表时间：
2005-12-05
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为了检测尚未识别的造血干细胞（hsc）特异性细胞表面分子，我们成功地将一种改进的信号序列陷阱应用于小鼠骨髓（BM） CD34−c-Kit+Sca-1+Lin−(CD34−KSL) hsc。其中鉴定出的分子之一，内啡肽，是一种与CD34密切相关的内皮分泌蛋白。Endomucin的高水平表达仅限于BM KSL hsc和祖细胞，重要的是，长期再生(LTR) - hsc仅存在于Endomucin+CD34−KSL群体中。值得注意的是，在卵黄囊中，在CD41（一种早期胚胎造血标志物）阳性的细胞片段中，Endomucin的表达将多能造血细胞从固定的红系祖细胞中分离出来。此外，胚胎内主动脉-性腺-中肾（AGM）区域的造血干细胞在妊娠10.5天（E10.5）和E11.5天（CD45+CD41+Endomucin+）的CD45−CD41+Endomucin+片段中高度富集。对这些部分的详细分析揭示了在这一狭窄的时间框架内，它们的骨髓再生能力以及体外细胞因子反应性发生了巨大变化。我们的研究结果确立了Endomucin作为ltr -HSC在整个发育过程中的一种新的细胞表面标记物，并为理解HSC的形成提供了有力的工具。
To detect as yet unidentified cell-surface molecules specific to hematopoietic stem cells (HSCs), a modified signal sequence trap was successfully applied to mouse bone marrow (BM) CD34−c-Kit+Sca-1+Lin− (CD34−KSL) HSCs. One of the identified molecules, Endomucin, is an endothelial sialomucin closely related to CD34. High-level expression of Endomucin was confined to the BM KSL HSCs and progenitor cells, and, importantly, long-term repopulating (LTR)–HSCs were exclusively present in the Endomucin+CD34−KSL population. Notably, in the yolk sac, Endomucin expression separated multipotential hematopoietic cells from committed erythroid progenitors in the cell fraction positive for CD41, an early embryonic hematopoietic marker. Furthermore, developing HSCs in the intraembryonic aorta-gonad-mesonephros (AGM) region were highly enriched in the CD45−CD41+Endomucin+ fraction at day 10.5 of gestation (E10.5) and in the CD45+CD41+Endomucin+ fraction at E11.5. Detailed analyses of these fractions uncovered drastic changes in their BM repopulating capacities as well as in vitro cytokine responsiveness within this narrow time frame. Our findings establish Endomucin as a novel cell-surface marker for LTR-HSCs throughout development and provide a powerful tool in understanding HSC ontogeny.