SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity
SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity
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DOI：
10.1182/blood-2005-05-2140
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发表时间：
2006-02-01
期刊：
影响因子：
20.3
通讯作者：
Morrison, SJ
中科院分区：
文献类型：
--
作者：
Yilmaz, OH;Kiel, MJ;Morrison, SJ
最近的进展提高了从幼鼠骨髓中分离的造血干细胞(HSCs)的纯度。然而，很少有人关注来自其他环境的造血干细胞的纯度。尽管来自年轻骨髓的Thy-1(Low)SCA-1(+)谱系(-)c-kit(+)细胞对HSCs高度浓缩(5个细胞中有1个细胞在移植到受照射的小鼠后可以进行长期的多系重建)，但来自老龄、重建或细胞因子动员的相同群体的小鼠的移植效率要低得多(185个细胞中有11个细胞可以实现长期的多系重建)。为了测试我们是否可以提高从这些环境中分离的HSCs的纯度，我们检查了SLAM家族标记CD150和CD48。所有从老年、重建和环磷酰胺/G-CSF动员的小鼠身上检测到的HSC都是CD150(+)CD48(-)，就像在正常的年轻骨髓中一样。THY-1(低)Sca1(+)谱系(-)c-kit(+)细胞主要包括缺乏重建能力的CD48(+)和/或CD150(-)细胞。来自老年、重组或动员小鼠的CD150(+)CD48(-)SCA-1(+)谱系(-)c-kit(+)细胞对HSCs的浓缩程度要高得多，每3到7个细胞中就有1个细胞能够进行长期的多谱系重建。SLAM家族受体的表达在不同环境中的HSC中是保守的，而来自老年、重组和动员的小鼠的HSCs在移植后当污染细胞被清除时相对有效地植入。
Recent advances have increased the purity of hematopoietic stem cells (HSCs) isolated from young mouse bone marrow. However, little attention has been paid to the purity of HSCs from other contexts. Although Thy-1(low)Sca-1(+)Lineage(-)c-kit(+) cells from young bone marrow are highly enriched for HSCs (1 in 5 cells gives long-term multilineage reconstitution after transplantation into irradiated mice), the same population from old, reconstituted, or cytokine-mobilized mice engrafts much less efficiently (11 in 78 to I in 185 cells gives long-term multilineage reconstitution). To test whether we could increase the purity of HSCs isolated from these contexts, we examined the SLAM family markers CD150 and CD48. All detectable HSCs from old, reconstituted, and cyclophosphamide/G-CSF-mobilized mice were CD150(+)CD48(-), just as in normal young bone marrow. Thy-1(low)Sca1(+)Lineage(-)c-kit(+) cells from old, reconstituted, or mobilized mice included mainly CD48(+) and/or CD150(-) cells that lacked reconstituting ability. CD150(+)CD48(-)Sca-1(+)Lineage(-)c-kit(+) cells from old, reconstituted, or mobilized mice were much more highly enriched for HSCs, with 1 in 3 to 1 in 7 cells giving long-term multilineage reconstitution. SLAM family receptor expression is conserved among HSCs from diverse contexts, and HSCs from old, reconstituted, and mobilized mice engraft relatively efficiently after transplantation when contaminating cells are eliminated.