McKenzie Joby L, Gan Olga I, Doedens Monica, Wang Jean C Y, Dick John E
Division of Cell and Molecular Biology, University Health Network, University of Toronto, Ontario M5G 1L7, Canada.
Nat Immunol. 2006 Nov;7(11):1225-33. doi: 10.1038/ni1393. Epub 2006 Oct 1.
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.
造血作用需要对造血干细胞（HSC）群体进行严格调控；然而，稳态下HSC的使用动态尚不确定。在3至7个月的时间里，我们评估了600多个个体人类“重症联合免疫缺陷小鼠重建造血细胞”（SRC）在连续移植的免疫缺陷小鼠中的再增殖和自我更新情况，这些细胞基于慢病毒整合位点进行追踪，同时也评估了迁移到同一只小鼠不同骨髓位置的SRC子代细胞的情况。我们的数据表明，在经历初始的克隆不稳定期后，自我更新的SRC可实现维持，这一结果与克隆更替模型不一致。我们发现SRC之间以及等效重建造血的SRC子代细胞之间的增殖动力学和自我更新存在广泛差异，这表明在SRC进入更严格的“下游”发育程序之前，其命运是不可预测的。
