SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells

SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells
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DOI:
10.1016/j.cell.2005.05.026
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发表时间:
2005-07-01
期刊:
影响因子:
64.5
通讯作者:
Morrison, SJ
Morrison, SJ
中科院分区:
生物学1区
文献类型:
--
作者:
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ

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为了提高我们鉴定造血干细胞(hsc)及其在体内定位的能力,我们比较了高度纯化的hsc和非自我更新的多能造血祖细胞(MPPs)的基因表达谱。SLAM家族的细胞表面受体,包括CD150、CD244和CD48,在功能不同的祖细胞中表达差异。造血干细胞高度纯化为CD150(+)CD244(-)CD48(-)细胞,mpp为CD244(+)CD150(-) CD48(-),大多数限制性祖细胞为CD48(+)CD244(+)CD150(-)。因此,可以根据所表达的SLAM家族成员的组合来预测造血祖细胞的原始性。这是第一个受体家族,其组合表达能精确区分干细胞和祖细胞。基于SLAM受体的简单组合纯化造血干细胞的能力使我们能够在组织切片中鉴定造血干细胞。许多造血干细胞与脾脏和骨髓的窦内皮相关,尽管一些造血干细胞与内皮相关。因此,造血干细胞占据了多个利基,包括不同组织中的窦状内皮。
To improve our ability to identify hematopoletic stem cells (HSCs) and their localization in vivo, we compared the gene expression profiles of highly purified HSCs and non-self-renewing multipotent hematopoletic progenitors (MPPs). Cell surface receptors of the SLAM family, including CD150, CD244, and CD48, were differentially expressed among functionally distinct progenitors. HSCs were highly purified as CD150(+)CD244(-)CD48(-) cells while MPPs were CD244(+) CD150(-)CD48(-) and most restricted progenitors were CD48(+)CD244(+)CD150(-). The primitiveness of hematopoietic progenitors could thus be predicted based on the combination of SLAM family members they expressed. This is the first family of receptors whose combinatorial expression precisely distinguishes stem and progenitor cells. The ability to purify HSCs based on a simple combination of SLAM receptors allowed us to identify HSCs in tissue sections. Many HSCs were associated with sinusoidal endothelium in spleen and bone marrow, though some HSCs were associated with endosteum. HSCs thus occupy multiple niches, including sinusoldal endothelium in diverse tissues.