The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation
The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation
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DOI：
10.1016/j.stem.2008.01.001
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发表时间：
2008-03-01
期刊：
影响因子：
23.9
通讯作者：
Mikkola, Hanna K. A.
中科院分区：
文献类型：
--
作者：
Rhodes, Katrin E.;Gekas, Christos;Mikkola, Hanna K. A.
小鼠胎盘是造血干细胞（HSCs）的重要储存库，但胎盘HSCs的来源尚不清楚。通过Runx 1-lacZ和CD 41的表达追踪发育中的HSC，我们发现HSC出现在胎盘的大血管中。对缺乏心跳的Ncx 1（-/-）胚胎的分析证实，HSC的发育是在胎盘血管系统中启动的，与血流无关。然而，在Ncx 1（-/-）胎盘中发现的CD 41+造血细胞比对照组少，这意味着一些HSC/祖细胞通过循环定殖胎盘和/或HSC出现在没有血流的情况下受到损害。重要的是，来自Ncx 1（-/-）胚胎的胎盘在外植体培养时具有产生骨髓红细胞和B和T淋巴细胞的同等潜力，验证了完整的多谱系造血潜力，这是发育HSC的特征。这些数据表明，除了在肝定殖之前为大量HSC提供小生境之外，胎盘是HSC产生的真正位点。
The mouse placenta was unveiled as an important reservoir for hematopoietic stem cells (HSCs), yet the origin of placental HSCs was unknown. By tracking developing HSCs by expression of Runx1-lacZ and CD41, we have found that HSCs emerge in large vessels in the placenta. Analysis of Ncx1(-/-) embryos, which lack a heartbeat, verified that HSC development is initiated in the placental vasculature independent of blood flow. However, fewer CD41+ hematopoietic cells were found in Ncx1(-/-) placentas than in controls, implying that some HSCs/progenitors colonize the placenta via circulation and/or HSC emergence is compromised without blood flow. Importantly, placentas from Ncx1(-/-) embryos possessed equal potential to generate myeloerythroid and B and T lymphoid cells upon explant culture, verifying intact multilineage hematopoietic potential, characteristic of developing HSCs. These data suggest that, in addition to providing a niche for a large pool of HSCs prior to liver colonization, the placenta is a true site of HSC generation.