Linkage between dendritic and T cell commitments in human circulating hematopoietic progenitors.

Linkage between dendritic and T cell commitments in human circulating hematopoietic progenitors.
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DOI:
10.4049/jimmunol.1303260
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发表时间:
2014-06-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Kusunoki Y
Kusunoki Y
中科院分区:
其他
文献类型:
--
作者:
Kyoizumi S;Kubo Y;Kajimura J;Yoshida K;Hayashi T;Nakachi K;Young LF;Moore MA;van den Brink MR;Kusunoki Y

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树突状细胞(DC)和T细胞在人类造血干细胞中的定向之间的关系还没有很好的理解。在这项研究中,我们计数和表征常规DC(cDC)和浆细胞样DC(pDC)前体与T细胞和胸腺衍生类型的NK细胞前体之间的CD 34+造血祖细胞(HPC)在人外周血(PB)循环。通过与表达Notch 1配体的基质细胞共培养的有限稀释分析,发现在健康供体中,HPC中DC的前体频率(PF)与T细胞PF显著相关,但与NK细胞PF无关。克隆分析表明,大多数T/NK-双重和T-单一谱系前体-但只有少数NK-单一谱系前体-与DC后代的产生相关。所有产生DC和T细胞后代的克隆均发现具有单核细胞和/或粒细胞后代,表明DC通过髓样DC途径分化。PB HPC亚群的分析显示,DC和T/NK细胞祖细胞之间的谱系分裂发生在分叉成T细胞谱系和NK细胞谱系之前的阶段。研究结果表明,DC和T细胞承诺之间存在强烈的联系,这可能是印记在循环淋巴启动的多能祖细胞或更上游的HPC。
The relationships between commitments of dendritic cells (DCs) and T cells in human hematopoietic stem cells are not well-understood. In this study, we enumerate and characterize conventional-DC (cDC) and plasmacytoid-DC (pDC) precursors in association with T-cell and thymus-derived types of NK-cell precursors among CD34+ hematopoietic progenitor cells (HPCs) circulating in human peripheral blood (PB). By limiting-dilution analyses using co-culture with stroma cells expressing Notch1 ligand, the precursor frequencies (PFs) of DCs in HPCs were found to significantly correlate with T-cell PFs, but not with NK-cell PFs, among healthy donors. Clonal analyses showed that the majority of T/NK-dual and T-single lineage precursors - but only a minority of NK-single lineage precursors - were associated with the generation of DC progenies. All clones producing both DC and T-cell progenies were found with monocyte and/or granulocyte progenies, suggesting DC differentiation via myeloid DC pathways. Analyses of PB HPC subpopulations revealed that the lineage split between DC and T/NK-cell progenitor occurs at the stage prior to bifurcation into T- and NK-cell lineages. The findings suggest a strong linkage between DC and T-cell commitments, which may be imprinted in circulating lymphoid-primed multipotent progenitors or in more upstream HPCs.
DOI: 10.4049/jimmunol.1203189
发表时间: 2013-06-15
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Kyoizumi S;Kubo Y;Kajimura J;Yoshida K;Imai K;Hayashi T;Nakachi K;Young LF;Moore MA;van den Brink MR;Kusunoki Y
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