Induction of T-cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro
Induction of T-cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro
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DOI：
10.1182/blood-2004-04-1293
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发表时间：
2005-02-15
期刊：
影响因子：
20.3
通讯作者：
Zúñiga-Pflücker, JC
中科院分区：
文献类型：
--
作者：
La Motte-Mohs, RN;Herer, E;Zúñiga-Pflücker, JC
Notch信号通路在T淋巴细胞分化的几个阶段起关键作用。然而，仍不清楚Notch配体Delta-like 1诱导的信号是否可以在体外支持来自确定来源的人造血干细胞（HSC）的完全T细胞分化。在这里，我们表明，人脐带血来源的造血干细胞培养的Delta样1表达OP 9基质细胞进行有效的T细胞谱系承诺和持续的T细胞分化。观察到T细胞发育的正常阶段特异性程序，包括产生携带CD 4和CD 8 α-T细胞受体（TCR）的细胞。T细胞分化的诱导依赖于OP 9细胞的Delta样1的表达。通过TCR接合刺激体外分化的T细胞诱导T细胞活化标志物和共刺激受体的表达。这些结果建立了一个有效的体外共培养系统，用于从人HSC产生T细胞，为研究早期T细胞分化和功能提供了新的途径。(C)2005年，美国血液学会。
The Notch signaling pathway plays a key role at several stages of T-lymphocyte differentiation. However, it remained unclear whether signals induced by the Notch ligand Delta-like 1 could support full T-cell differentiation from a defined source of human hematopoietic stem cells (HSCs) in, vitro. Here, we show that human cord blood-derived HSCs cultured on Delta-like 1-expressing OP9 stromal cells undergo efficient T-cell lineage commitment and sustained T-cell differentiation. A normal stage-specific program of T-cell development was observed, including the generation of CD4 and CD8 alphabeta-T-cell receptor (TCR)-bearing cells. Induction of T-cell differentiation was dependent on the expression of Delta-like 1 by the OP9 cells. Stimulation of the in vitro-differentiated T cells by TCR engagement induced the expression of T-cell activation markers and costimulatory receptors. These results establish an efficient in vitro coculture system for the generation of T cells from human HSCs, providing a new avenue for the study of early T-cell differentiation and function. (C) 2005 by The American Society of Hematology.