Effects of thymic polypeptides on the thymopoiesis of mouse embryonic stem cells

被引:30
|
作者
Peng, Yanwen [1 ,2 ]
Chen, Zhenguang [4 ]
Yu, Weihua [1 ]
Zhou, Qifeng [3 ]
Xu, Lin [1 ,2 ]
Mao, Frank Fuxiang [1 ]
Huang, Gang [4 ]
Zhang, Xiuming [1 ]
Li, Shunong [1 ]
Lahn, Bruce T. [1 ]
Xiang, Andy Peng [1 ]
机构
[1] Sun Yat Sen Univ, Ctr Stem Cell Biol & Tissue Engn, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Sch Preclin Med, Dept Immunol, Guangzhou 510080, Guangdong, Peoples R China
[3] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[4] Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China
关键词
Embryonic stem (ES) cells; T cells; Thymopentin (TP5); Thymosin alpha-1 (T alpha-1); Thymopeptides;
D O I
10.1016/j.cellbi.2008.07.011
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The thymus provides a unique cellular and hormonic microenvironment for the development of immunocompetent T cells. Thymic polypeptides have been widely used clinically for the treatment of tumors, infectious diseases and immune deficiency diseases. They have already shown the ability to stimulate the maturation of hematopoietic stem cells towards the CD3+CD4+ T cell lineage. However, their effects on the thymopoiesis of embryonic stem cells are still unexplored. In this paper, we compared the effects of three thymic polypeptides, thymopentin (TP5), thymosin alpha-1 (T alpha-1) and thymopeptides on the in vitro thymopoiesis of mouse embryonic stem (ES) cells. Using the embryoid body induction system, we found that both T alpha-1 and thymopeptides effectively induced ES cells to differentiate sequentially into the CD3+ and CD4+/CD8+ T cells. These T cells had T cell receptor (TCR) V beta gene rearrangement and most were TCR alpha beta T cells. We also found that the expression of the Notch receptor and its ligands Delta-like-1 and Delta-like-4 gradually increased during the induction. However, TP5 failed to induce the T cell differentiation of the ES cells. In summary, this is the first report to demonstrate that T alpha-1 can stimulate the T cell early stage differentiation from ES cells using the embryoid body protocol. These findings provide a powerful model for studying T cell development and may open new venues for the clinical application of T alpha-1. (c) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1265 / 1271
页数:7
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