Lin-Sca1+kit- bone marrow cells contain early lymphoid-committed precursors that are distinct from common lymphoid progenitors.
Lin-Sca1+kit- bone marrow cells contain early lymphoid-committed precursors that are distinct from common lymphoid progenitors.
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DOI：
10.4049/jimmunol.181.11.7507
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发表时间：
2008-12-01
期刊：
影响因子：
--
通讯作者：
Snoeck HW
中科院分区：
文献类型：
--
作者：
Kumar R;Fossati V;Israel M;Snoeck HW
据报道，谱系阴性、Sca1阳性、c-kit阴性（LSK-）细胞在小鼠骨髓中缺乏长期再生能力或骨髓潜能，其意义尚不清楚。在这里，我们发现LSK-群体由flt3、CD25和IL7Rα的表达定义的几个亚群组成。第一个亚群是CD25-，超过90%表达flt3、IL7Rα或两者兼而有。CD25-LSK-群体在体内具有T、B和NK细胞潜能，且这种活性大部分局限于flt3+亚群，与IL7Rα的表达无关。flt3+LSK-细胞在体内的淋巴样电位比lin- sc1lokitloil7r α+普通淋巴样祖细胞（CLPs）低3倍，但其体外克隆效率比CLPs低10倍。此外，虽然在缺乏M-CSF的情况下，flt3+LSK-细胞的髓细胞电位比CLPs低10倍，但在M-CSF存在时，两种细胞的相对髓细胞电位相似。这些观察结果表明，两种人群对生长因子的需求不同。LSK-细胞的第二个亚群是CD25++flt3-IL7Rα+，可以从CD25-LSK-细胞和CLPs中产生，但不能移植到免疫缺陷的Rag1-/-或Rag1-/-γc-/-宿主中。该种群在Rag1-/-小鼠和老年小鼠中增加，其意义尚不清楚。因此，LSK-群体在表型和功能上是异质的，并且包含早期淋巴细胞前体。我们的研究结果表明，淋巴细胞承付的早期阶段比迄今认为的要复杂得多。
The significance of a population in mouse bone marrow of lineage negative, Sca1 positive, c-kit negative (LSK-) cells, which is reported to be devoid of long-term repopulation capacity or myeloid potential, is unknown. Here, we show that the LSK- population is composed of several subsets defined by the expression of flt3, CD25 and IL7Rα. The first subset was CD25- and more than 90 % expressed either flt3, IL7Rα or both. The CD25-LSK- population had T, B and NK cell potential in vivo, and most of this activity was localized in the flt3+ subset, irrespective of the expression of IL7Rα. While lymphoid potential of flt3+LSK- cells in vivo was threefold lower than that of lin-Sca1lokitloIL7Rα+ common lymphoid progenitors (CLPs), their cloning efficiency in vitro was tenfold lower than that of CLPs. Furthermore, while the myeloid potential of flt3+LSK- cells was tenfold lower than that of CLPs in the absence of M-CSF, the relative myeloid potential of both population was similar in its presence. These observations suggest differential growth factor requirements of both populations. The second subset of LSK- cells was homogeneously CD25++flt3-IL7Rα+ and could be generated from both CD25-LSK- cells and from CLPs, but did not engraft in immunodeficient Rag1-/- or Rag1-/-γc-/- hosts. This population, of which the significance is unclear, was increased in Rag1-/- mice and in old mice. Thus, the LSK- population is phenotypically and functionally heterogeneous and contains early lymphoid-committed precursors. Our findings imply that the early stages of lymphoid commitment are more complex than was thus far assumed.
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影响因子：
32.4
作者：
Igarashi, H;Gregory, SC;Kincade, PW
通讯作者：
Kincade, PW
影响因子：
64.5
作者：
Adolfsson, J;Månsson, R;Jacobsen, SEW
通讯作者：
Jacobsen, SEW
影响因子：
4.4
作者：
Miller, JP;Allman, D
通讯作者：
Allman, D
DOI：
10.1084/jem.20060697
发表时间：
2006-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
32.4
作者：
Schmitt, TM;Zúñiga-Pflücker, JC
通讯作者：
Zúñiga-Pflücker, JC