SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors.
SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors.
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DOI：
10.1016/j.stem.2013.05.014
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发表时间：
2013-07-03
期刊：
影响因子：
23.9
通讯作者：
Morrison, Sean J.
中科院分区：
文献类型：
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作者：
Oguro, Hideyuki;Ding, Lei;Morrison, Sean J.
造血干细胞（HSC）和多能造血祖细胞（MPP）通常使用各种标记物分离，但仍然是异质的。在这里，我们表明，四个SLAM家族标志物，CD150，CD48，CD229和CD244，可以区分HSC和MPPs从限制祖细胞和细分成一个层次的功能不同的亚群细胞周期状态，自我更新和重建潜力的逐步变化。CD229表达在很大程度上区分了淋巴细胞偏向的HSC和很少分裂的骨髓偏向的HSC，使得能够前瞻性地富集这些HSC亚群。CD229和CD244表达的差异将CD150 − CD48 −/lowLineage −/lowSca-1 + c-Kit+细胞分解为高度纯化的MPP层级，这些MPP保留了红细胞和血小板潜能，但在有丝分裂活性和重建潜能方面表现出进行性变化。这些标记物的使用和重建试验表明，从内皮细胞和血管周围基质细胞中条件性删除Scf消除了绝大多数骨髓HSC，包括几乎所有的CD229-/低HSC，表明静止的HSC由血管周围的小生境维持。
Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitors (MPPs) are routinely isolated using various markers but remain heterogeneous. Here we show that four SLAM family markers, CD150, CD48, CD229, and CD244, can distinguish HSCs and MPPs from restricted progenitors and subdivide them into a hierarchy of functionally distinct subpopulations with stepwise changes in cell-cycle status, self-renewal, and reconstituting potential. CD229 expression largely distinguished lymphoid-biased HSCs from rarely-dividing myeloid-biased HSCs, enabling prospective enrichment of these HSC subsets. Differences in CD229 and CD244 expression resolved CD150−CD48−/lowLineage−/lowSca-1+c-Kit+ cells into a hierarchy of highly-purified MPPs that retained erythroid and platelet potential but exhibited progressive changes in mitotic activity and reconstituting potential. Use of these markers, and reconstitution assays, showed that conditional deletion of Scf from endothelial cells and perivascular stromal cells eliminated the vast majority of bone marrow HSCs, including nearly all CD229−/low HSCs, demonstrating that quiescent HSCs are maintained by a perivascular niche.
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