CLONAL AND SYSTEMIC ANALYSIS OF LONG-TERM HEMATOPOIESIS IN THE MOUSE
CLONAL AND SYSTEMIC ANALYSIS OF LONG-TERM HEMATOPOIESIS IN THE MOUSE
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DOI：
10.1101/gad.4.2.220
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发表时间：
1990-02-01
影响因子：
10.5
通讯作者：
LEMISCHKA, IR
中科院分区：
文献类型：
--
作者：
JORDAN, CT;LEMISCHKA, IR
我们分析了63只重组小鼠的142个个体干细胞克隆在体内的时间命运。从移植了遗传标记干细胞的动物身上获得的四种主要外周血系的长期序列分析表明，发育行为主要是时间的函数。因此，移植后的头4-6个月的特点是干细胞增殖和分化行为的频繁波动。渐渐地，一个稳定的造血系统出现了，由少数的全能性克隆主导。我们证明了单个干细胞克隆足以在动物的一生中维持造血功能，并表明单克隆或少克隆可能是长期重建系统的标志。提出了一个模型，其中谱系限制分化和戏剧性的克隆通量是作用于不断扩大的全能性细胞池的机制的结果，并不表明本质上不同的干细胞类别。
We have analyzed the temporal in vivo fate of 142 individual stem cell clones in 63 reconstituted mice. Long-term sequential analyses of the four major peripheral blood lineages, obtained from animals engrafted with genetically marked stem cells, indicate that developmental behavior is primarily a function of time. As such, the first 4-6 months post-engraftment is characterized by frequent fluctuations in stem cell proliferation and differentiation behavior. Gradually, a stable hematopoietic system emerges, dominated by a small number of totipotent clones. We demonstrate that single stem cell clones are sufficient to maintain hematopoiesis over the lifetime of an animal and suggest that mono- or oligoclonality may be a hallmark of long-term reconstituted systems. A model is proposed, wherein lineage-restricted differentiation and dramatic clonal flux are consequences of mechanisms acting on an expanding pool of totipotent cells and are not indicative of intrinsically distinct stem cell classes.