Induction of T cell development and establishment of T cell competence from embryonic stem cells differentiated in vitro
Induction of T cell development and establishment of T cell competence from embryonic stem cells differentiated in vitro
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DOI：
10.1038/ni1055
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发表时间：
2004-04-01
影响因子：
30.5
通讯作者：
Zúñiga-Pflücker, JC
中科院分区：
文献类型：
--
作者：
Schmitt, TM;de Pooter, RF;Zúñiga-Pflücker, JC
胚胎干细胞（ESCs）具有作为可移植组织特异性干细胞的可再生来源的潜力。然而，指导胚胎干细胞向特定细胞谱系分化所需的分子线索仍然不清楚。在这里，我们报告成功地诱导ESC分化为成熟的功能性T淋巴细胞与一个简单的体外共培养系统。ESC向T细胞的定向分化需要Notch受体与在OP 9-DL 1基质细胞系上表达的Delta样1配体（DL 1）的接合。我们发现在ESC-OP 9-DL 1细胞共培养物中T细胞分化的正常程序。ESC衍生的T细胞祖细胞有效地重建了免疫缺陷小鼠的T细胞区室，从而能够有效地响应病毒感染。这些发现为T细胞发育的分子分析提供了强有力的工具，并为使用确定的干细胞来源开发免疫方法开辟了新途径。
Embryonic stem cells (ESCs) have the potential to serve as a renewable source of transplantable tissue-specific stem cells. However, the molecular cues necessary to direct the differentiation of ESCs toward specific cell lineages remain obscure. Here we report the successful induction of ESC differentiation into mature functional T lymphocytes with a simple in vitro coculture system. The directed differentiation of ESCs into T cells required the engagement of Notch receptors by Delta-like 1 ligand (DL1) expressed on the OP9-DL1 stromal cell line. We found a normal program of T cell differentiation in ESC-OP9-DL1 cell cocultures. ESC-derived T cell progenitors effectively reconstituted the T cell compartment of immunodeficient mice, enabling an effective response to a viral infection. These findings provide a powerful tool for the molecular analysis of T cell development and open new avenues for the development of immunotherapeutic approaches using defined sources of stem cells.