Long-term propagation of distinct hematopoietic differentiation programs in vivo
Long-term propagation of distinct hematopoietic differentiation programs in vivo
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DOI：
10.1016/j.stem.2007.05.015
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发表时间：
2007-08-01
期刊：
影响因子：
23.9
通讯作者：
Eaves, Connie
中科院分区：
文献类型：
--
作者：
Dykstra, Brad;Kent, David;Eaves, Connie
造血干细胞分化行为的异质性已被充分记录，但人们对其了解甚少。为了在克隆水平上研究这个问题，我们分离了一个成年小鼠骨髓亚群，该亚群高度富集于体内多系再生细胞，并将其作为单细胞或其在体外产生的短期克隆后代移植到352名受体中。在这些小鼠中，有93只小鼠在至少4个月的时间里以四种不同模式中的一种表现出供体来源的循环白细胞贡献。一系列移植实验表明，其中两种模式与移植的原始细胞的广泛自我更新有关。然而，在体外4天内，随后在体内获得的再生模式以克隆特异性的方式转移到骨髓贡献较少的克隆。因此，原始造血细胞可以在体内连续移植后保持独特的再生特性，尽管这些特性在体外也会迅速改变。
Heterogeneity in the differentiation behavior of hematopoietic stem cells is well documented but poorly understood. To investigate this question at a clonal level, we isolated a subpopulation of adult mouse bone marrow that is highly enriched for multilineage in vivo repopulating cells and transplanted these as single cells, or their short-term clonal progeny generated in vitro, into 352 recipients. Of the mice, 93 showed a donor-derived contribution to the circulating white blood cells for at least 4 months in one of four distinct patterns. Serial transplantation experiments indicated that two of the patterns were associated with extensive self-renewal of the original cell transplanted. However, within 4 days in vitro, the repopulation patterns subsequently obtained in vivo shifted in a clone-specific fashion to those with less myeloid contribution. Thus, primitive hematopoietic cells can maintain distinct repopulation properties upon serial transplantation in vivo, although these properties can also alter rapidly in vitro.