title: Effects of thymic polypeptides on the thymopoiesis of mouse embryonic stem cells.
abstract: 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.
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, 74# Zhongshan Road 2, Guangzhou, Guangdong 510080, PR China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Peng
authors.forename: Zhenguang
authors.initials: Z
authors.lastname: Chen
authors.forename: Weihua
authors.initials: W
authors.lastname: Yu
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Frank Fuxiang
authors.initials: FF
authors.lastname: Mao
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Xiuming
authors.initials: X
authors.lastname: Zhang
authors.forename: Shunong
authors.initials: S
authors.lastname: Li
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Lahn
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: 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
chemical_list: D017252:CD3 Complex; D051881:Receptor, Notch1; D011948:Receptors, Antigen, T-Cell; D051880:Receptors, Notch; D013947:Thymosin; D016305:Thymopentin; D000077596:Thymalfasin