Effects of thymic polypeptides on the thymopoiesis of mouse embryonic stem cells.
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 (Talpha-1) and thymopeptides on the in vitro thymopoiesis of mouse embryonic stem (ES) cells. Using the embryoid body induction system, we found that both Talpha-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) Vbeta gene rearrangement and most were TCRalphabeta 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 Talpha-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 Talpha-1.
Peng
Yanwen
Y
Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, 74# Zhongshan Road 2, Guangzhou, Guangdong 510080, PR China.
Chen
Zhenguang
Z
Yu
Weihua
W
Zhou
Qifeng
Q
Xu
Lin
L
Mao
Frank Fuxiang
FF
Huang
Gang
G
Zhang
Xiuming
X
Li
Shunong
S
Lahn
Bruce T
BT
Xiang
Andy Peng
AP
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D000077596:Thymalfasin; D016305:Thymopentin / Q000378:metabolism / Q000494:pharmacology*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013950:Thymus Gland / Q000378:metabolism / Q000502:physiology
D017252:CD3 Complex; D051881:Receptor, Notch1; D011948:Receptors, Antigen, T-Cell; D051880:Receptors, Notch; D013947:Thymosin; D016305:Thymopentin; D000077596:Thymalfasin