Dormant and self-renewing hematopoietic stem cells and their niches
Dormant and self-renewing hematopoietic stem cells and their niches
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DOI：
10.1196/annals.1392.021
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Trumpp, Andreas
中科院分区：
文献类型：
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作者：
Wilson, Anne;Oser, Gabriela M.;Trumpp, Andreas
在小鼠中，在过去的20年中，一组细胞表面标记物和活性已经被确定，从而能够分离出高度富集造血干细胞（hsc）的骨髓（BM）群体。这些造血干细胞有能力产生多个谱系，并具有长期的自我更新能力，因此在移植到致命辐射受体后，它们能够重建并维持一个功能性的造血系统。使用单细胞重组测定，可以使用各种标记组合来获得几乎50%的功能性HSC纯度。在这里，我们使用六种标记物（Seal, e-Kit, CD135, CD48， CD150和CD34）在谱系缺失的BM上的差异表达来完善HSC群体中的细胞等级。在层次结构的顶端，我们提出了一个休眠的HSC群体(Lin(-)Sea1(+)c-Kit(+) CD48(-)CD150(+)CD34(-))，它产生了一个活跃的自我更新的CD34(+) HSC群体。造血干细胞的休眠，以及自我更新和分化活动之间的平衡，至少在一定程度上是由单个造血干细胞附着的干细胞壁龛控制的。在这里，我们回顾了目前关于造血干细胞壁龛的知识，并提出休眠的造血干细胞位于内皮的壁龛中，而激活的造血干细胞与基底动脉微血管的窦状面密切接触。
In the mouse, over the last 20 years, a set of cell-surface markers and activities have been identified, enabling the isolation of bone marrow (BM) populations highly enriched in hematopoietic stem cells (HSCs). These HSCs have the ability to generate multiple lineages and are capable of long-term self-renewal activity such that they are able to reconstitute and maintain a functional hematopoietic system after transplantation into lethally irradiated recipients. Using single-cell reconstitution assays, various marker combinations can be used to achieve a functional HSC purity of almost 50%. Here we have used the differential expression of six of these markers (Seal, e-Kit, CD135, CD48, CD150, and CD34) on lineage-depleted BM to refine cell hierarchies within the HSC population. At the top of the hierarchy, we propose a dormant HSC population (Lin(-)Sea1(+)c-Kit(+) CD48(-)CD150(+)CD34(-)) that gives rise to an active self-renewing CD34(+) HSC population. HSC dormancy, as well as the balance between self-renewal and differentiation activity, is at least, in part, controlled by the stem cell niches individual HSCs are attached to. Here we review the current knowledge about HSC niches and propose that dormant HSCs are located in niches at the endosteum, whereas activated HSCs are in close contact to sinusoids of the BM microvasculature.