Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages
Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages
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DOI：
10.1182/blood-2007-11-126219
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发表时间：
2008-06-15
期刊：
影响因子：
20.3
通讯作者：
Weissman, Irving L.
中科院分区：
文献类型：
--
作者：
Karsunky, Holger;Inlay, Matthew A.;Weissman, Irving L.
成熟的血细胞由多能造血干细胞通过一系列连续的中间体发育而成，其中特定血统的发育潜力逐渐消失。我们之前报道了这些发育中间体之一的鉴定，即共同淋巴祖细胞 (CLIP)，它可以产生 T 细胞、B 细胞、树突状细胞 (DC) 和自然杀伤细胞 (NK)，但缺乏骨髓和红细胞潜能。最近，一些研究表明 CLP 的 T 细胞和 DC 潜力有限或不存在，和/或 CLP 含有显着的骨髓潜力。在这里，我们证明最初确定的 CLIP 群体可以根据酪氨酸激酶受体 Flk2 的表达分为功能不同的子集。 Flk2(+) 子集含有强大的体内和体外 T 细胞、B 细胞、DC 和 NK 潜能，但缺乏骨髓潜能，因此代表寡能、淋巴限制性祖细胞。该细胞群似乎不偏向 B 细胞，并且在体内稳健地重建 B 和 T 谱系，这与其作为这两个亚群的生理祖细胞一致。因此，Flk2 表达定义了一个同质的、易于获得的骨髓 CLP 子集，该子集完全是淋巴定向的，并且可以同等程度地分化为 B 和 T 谱系。
Mature blood cells develop from multipotent hematopoietic stem cells through a series of sequential intermediates in which the developmental potential for particular blood lineages is progressively extinguished. We previously reported the identification of one of these developmental intermediates, the common lymphoid progenitor (CLIP), which can give rise to T cells, B cells, dendritic cells (DCs), and natural killer cells (NKs), but lacks myeloid and erythroid potential. Recently, several studies have suggested that the T-cell and DC potential of CLP is limited or absent, and/or that CLP contains significant myeloid potential. Here, we show that the originally identified CLIP population can be divided into functionally distinct subsets based on the expression of the tyrosine kinase receptor, Flk2. The Flk2(+) subset contains robust in vivo and in vitro T-cell, B-cell, DC, and NK potential, but lacks myeloid potential and, therefore, represents an oligopotent, lymphoid-restricted progenitor. This population of cells does not appear to be B cell-biased and robustly reconstitutes both B and T lineages in vivo, consistent with its being a physiologic progenitor of both of these subsets. Thus, Flk2 expression defines a homogeneous, readily obtainable subset of bone marrow CLP that is completely lymphoid-committed and can differentiate equivalently well into both B and T lineages.