Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment
Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment
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DOI：
10.1038/ni1393
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发表时间：
2006-11-01
影响因子：
30.5
通讯作者：
Dick, John E.
中科院分区：
文献类型：
--
作者：
McKenzie, Joby L.;Gan, Olga I.;Dick, John E.
造血需要造血干细胞（HSC）群体的严格调控;然而，HSC在稳态下的动态使用是不确定的。在3 - 7个月内，我们评估了超过600个个体的人“严重联合免疫缺陷小鼠再增殖细胞”（SRC）的再增殖和自我更新，这些细胞在连续移植的免疫缺陷小鼠中基于慢病毒整合位点进行追踪，以及SRC子细胞在单个小鼠中迁移到不同骨髓位置。我们的数据表明，自我更新SRCs维护后的克隆不稳定的初始阶段，结果与克隆演替模型不一致。我们发现SRC之间的增殖动力学和自我更新的变化很大，以及SRC子细胞之间的重新填充相等，这表明SRC的命运是不可预测的，然后SRC进入更严格的“下游”发展计划。
Hematopoiesis requires tight regulation of the hematopoietic stem cell ( HSC) population; however, the dynamics of HSC use at steady state are uncertain. Over 3 - 7 months, we evaluated the repopulation and self-renewal of more than 600 individual human 'severe combined immunodeficiency mouse - repopulating cells' ( SRCs), tracked on the basis of lentiviral integration sites, in serially transplanted immune-deficient mice, as well as of SRC daughter cells that migrated to different marrow locations in a single mouse. Our data demonstrate maintenance by self-renewing SRCs after an initial period of clonal instability, a result inconsistent with the clonal succession model. We found wide variation in proliferation kinetics and self-renewal among SRCs, as well as between SRC daughter cells that repopulated equivalently, suggesting that SRC fate is unpredictable before SRCs enter more rigid 'downstream' developmental programs.