Enhanced purification of fetal liver hematopoietic stem cells using SLAM family receptors
Enhanced purification of fetal liver hematopoietic stem cells using SLAM family receptors
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DOI：
10.1182/blood-2005-10-4135
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发表时间：
2006-07-15
期刊：
影响因子：
20.3
通讯作者：
Morrison, Sean J.
中科院分区：
文献类型：
--
作者：
Kim, Injune;He, Shenghui;Morrison, Sean J.
虽然成年小鼠的造血干细胞(HSCs)已经被纯化到近乎均一的水平，但用胎儿HSCs仍然不可能做到这一点。最近使用SLAM家族受体CD150、CD244和CD48提高了成人HSC的纯度。这些标记物在血息分级的不同阶段都有表达，因此有可能将成人HSCs高度纯化为CD150(+)CD48(-)CD244(-)细胞。我们发现SLAM家族受体在胎肝中表现出类似的表达模式。胎肝HSC为CD150(+)、CD48(-)、CD244(-)，绝大多数集落形成祖细胞为CD48(+)、CD244(-)、CD150(-)或CD48(+)、CD244(+)、CD150(-)，与成人骨髓一样。SLAM家族标志物可促进胎肝HSCs的纯化。而照射组每8.9个Thy(Low)Sca-1(+)细胞系中有1个(111%)出现长期多系重建，5.7个CD150(+)CD48(-)CD41(-)细胞和每2.7个CD150(+)CD48(-)Sca-1(+)系(-)Mac-1(+)胎肝细胞中有1个(37%)出现长期多系重建。这些数据强调了SLAM家族标记物在血息分级的不同阶段区分祖细胞的稳健性，并加强了来自不同环境的决定性HSC的纯化。然而，CD150、CD244和CD48不是泛干细胞标记物，因为它们不能被胎儿或成人神经系统中的干细胞检测到表达。
Although adult mouse hematopoletic stem cells (HSCs) have been purified to near homogeneity, it remains impossible to achieve this with fetal HSCs. Adult HSC purity recently has been enhanced using the SLAM family receptors CD150, CD244, and CD48. These markers are expressed at different stages of the hematopolesis hierarchy, making it possible to highly purify adult HSCs as CD150(+)CD48(-)CD244(-) cells. We found that SLAM family receptors exhibited a similar expression pattern in fetal liver. Fetal liver HSCs were CD150(+)CD48(-)CD244(-), and the vast majority of colony-forming progenitors were CD48(+)CD244(-)CD150(-) or CD48(+)CD244(+)CD150(-), just as in adult bone marrow. SLAM family markers enhanced the purification of fetal liver HSCs. Whereas 1 (111%) of every 8.9 Thy(low)Sca-1(+) lineage-Mac-1(+) fetal liver cells gave long-term multilineage reconstitution in irradiated mice, 1 (18%) of every 5.7 CD150(+)CD48(-)CD41(-) cells and 1 (37%) of every 2.7 CD150(+)CD48(-)Sca-1(+)lineage(-)Mac-1(+) fetal liver cells gave long-term multilineage reconstitution. These data emphasize the robustness with which SLAM family markers distinguish progenitors at different stages of the hematopolesis hierarchy and enhance the purification of definitive HSCs from diverse contexts. Nonetheless, CD150, CD244, and CD48 are not pan-stem cell markers, as they were not detectably expressed by stem cells in the fetal or adult nervous system.