Short exposure to Notch ligand Delta-4 is sufficient to induce T-cell differentiation program and to increase the T cell potential of primary human CD34+ cells
Short exposure to Notch ligand Delta-4 is sufficient to induce T-cell differentiation program and to increase the T cell potential of primary human CD34+ cells
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DOI：
10.1016/j.exphem.2006.08.007
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发表时间：
2006-12-01
影响因子：
2.6
通讯作者：
Levy, Yves
中科院分区：
文献类型：
--
作者：
Lefort, Nathalie;Benne, Clarisse;Levy, Yves
Objective. Notch通路在细胞命运选择和T细胞发育中起关键作用。我们研究的目的是评估Notch通路的体外短刺激是否可以改变人祖细胞的行为。将CD 34（+）脐带血祖细胞暴露于固定的Notch配体Delta-4或在对照条件下4天。在第4天评估由短刺激诱导的表型和分子变化。接下来，在适合于B（与MS 5基质细胞共培养）和T（表达Delta-4系统的FTOC和OP 9基质细胞）细胞分化的培养条件下评估这些祖细胞命运的长期改变。Notch激活足以触发与早期T细胞谱系分化一致的免疫表型和分子变化。Delta-4在4天内诱导CD + cytCD 3+细胞。这在基因转录水平上与几个T细胞相关的转录因子和TCR γ重排的从头表达有关，而同时B细胞转录物被沉默。与非Delta-4引发的细胞相比，这些早期变化转化为细胞潜力的长期改变。当细胞在适合T细胞发育的系统中培养时，Delta-4引发导致T细胞发育加速，包括TCR重排的完成，而B细胞发育被抑制。短暂的Notch激活足以促进脐带血CD 34（+）细胞向T细胞分化。该系统可能是一个有用的工具，用于扩增和定量的T电位的CD 34（+）细胞在各种疾病的条件。(c)2006年国际实验血液学学会。爱思唯尔公司出版
Objective. The Notch pathway plays a key role in cell fate choices and in T-cell development. The goal of our study was to evaluate whether a short in vitro stimulation of the Notch pathway may alter human progenitor cell behavior.Methods. CD34(+) cord blood progenitors were exposed for 4 days to either immobilized Notch ligand Delta-4 or in control conditions. Phenotypic and molecular changes induced by the short stimulation were assessed at day 4. Next, long-term alteration of the fate of these progenitors was assessed in culture conditions suitable for B (coculture with MS5 stromal cells) and T (FTOC and OP9 stromal cells expressing Delta-4 systems) cell differentiation.Results. Notch activation was sufficient to trigger immunophenotypic and molecular changes consistent with early T-cell lineage differentiation. Delta-4 induced, in 4 days, CD+'cytCD3 epsilon(+) cells. This paralleled at the gene-transcription level with de novo expression of several T cell-related transcription factors and TCR gamma rearrangement, while B cell transcripts were simultaneous silenced. As compared to non-Delta-4 primed cells, these early changes translated to long-term alteration of the potential of cells. Delta-4 priming led to an acceleration of T-cell development, including a completion of the TCR rearrangement, when cells were cultured in systems suitable for T-cell development while B-cell development was inhibited.Conclusion. A transient Notch activation is sufficient to promote T-cell differentiation from cord blood CD34(+) cells. This system may be a useful tool for the amplification and the quantification of the T potential of CD34(+) cells in various disease conditions. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.