title: Thymopentin enhances the generation of T-cell lineage derived from human embryonic stem cells in vitro.
abstract: Thymopentin is a group of biologically active peptide secreted mainly by the epithelial cells of thymic cortex and medulla. Whether it promotes T cells production from human embryonic stem cells(hESCs) in vitro remains an elusive issue. In the present study, we develop a novel strategy that enhances T-cell lineage differentiation of hESCs in collagen matrix culture by sequential cytokine cocktails treatment combined with thymopentin stimulation. We observed that approximately 30.75% cells expressed CD34 on day 14 of the cultures and expressed the surface markers of erythroid, lymphoid and myeloid lineages. The results of colony assays and gene expressions by RT-PCR analysis also demonstrated that hematopoietic progenitor cells (HPCs) derived from hESCs were capable of multi-lineage differentiation. Further study revealed that culturing with thymopentin treatment, the CD34(+)CD45RA(+)CD7(+) cells sorted from HPCs expressed T-cell-related genes, IKAROS, DNTT, TCRγ and TCRβ, and T-cell surface markers, CD3, cytoplasmic CD3, CD5, CD27, TCRγδ, CD4 and CD8. The differentiated cells produced the cytokines including IFN-γ, IL-2 and TNF-α in response to stimulation, providing the evidence for T-cell function of these cells. In conclusion, thymopentin enhances T-cell lineage differentiation from hESCs in vitro by mimicking thymus peptide environment in vivo.
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China; Department of Clinic Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: zhumingxia@bjmu.edu.cn.
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Zhu
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China; Department of Clinic Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: wanwenli110609@126.com.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Wan
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: lihaishen.happy@163.com.
authors.forename: Hai-Shen
authors.initials: HS
authors.lastname: Li
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: crystal_bmu@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Reproductive Medical Center, Peking University Third Hospital, Beijing 100191, PR China; Department of Clinic Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: Chenguian2008@bjmu.edu.cn.
authors.forename: Gui-An
authors.initials: GA
authors.lastname: Chen
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, PR China; Department of Clinic Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: xiaoyank@yahoo.com.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Ke
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis / Q000378:metabolism; D019011:Antigens, CD7 / Q000378:metabolism; D000954:Antigens, Surface / Q000096:biosynthesis; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D038041:Lymphopoiesis / Q000187:drug effects*; D039904:Pluripotent Stem Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*; D016305:Thymopentin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018952:Antigens, CD34; D019011:Antigens, CD7; D000954:Antigens, Surface; C508594:IL2 protein, human; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D016305:Thymopentin
keywords: Cell differentiation; Hematopoietic progenitor cells; Human embryonic stem cells\; T lymphocytes; Thymopentin