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Directed Differentiation of Human Embryonic Stem Cells into Thymic Epithelial Progenitor-like Cells Reconstitutes the Thymic Microenvironment In Vivo
Sun, Xiaoning1; Xu, Jun2; Lu, Hongxia2; Liu, Wang2; Miao, Zhenchuan2; Sui, Xin1,2; Liu, Haisong1; Su, Li4; Du, Weichao2; He, Qihua4; Chen, Fangyuan2; Shi, Yan1; Deng, Hongkui1,2,3
刊名CELL STEM CELL
2013-08-01
DOI10.1016/j.stem.2013.06.014
13期:2页:230-236
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell & Tissue Engineering ; Cell Biology
资助者National Basic Research Program of China (973 program) ; Key New Drug Creation and Manufacturing Program ; National Science and Technology Major Project ; Ministry of Science and Technology ; 111 project ; Bill &amp ; Melinda Gates Foundation ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation ; National Basic Research Program of China (973 program) ; Key New Drug Creation and Manufacturing Program ; National Science and Technology Major Project ; Ministry of Science and Technology ; 111 project ; Bill &amp ; Melinda Gates Foundation ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation
研究领域[WOS]Cell Biology
关键词[WOS]ENDODERM ; MICE ; ORGANOGENESIS ; GENERATION ; LUNG ; IDENTIFICATION ; INHIBITION ; MECHANISMS ; EXPRESSION ; TISSUE
英文摘要

Thymus transplantation has great clinical potential for treating immunological disorders, but the shortage of transplant donors limits the progress of this therapy. Human embryonic stem cells (hESCs) are promising cell sources for generating thymic epithelial cells. Here, we report a stepwise protocol to direct the differentiation of hESCs into thymic epithelial progenitor-like cells (TEPLCs) by mimicking thymus organogenesis with sequential regulation of Activin, retinoic acid, BMP, and WNT signals. The hESC-derived TEPLCs expressed the key thymic marker gene FOXN1 and could further develop in vivo into thymic epithelium expressing the functional thymic markers MHC II and AIRE upon transplantation. Moreover, the TEPLC-derived thymic epithelium could supportmouse thymopoiesis in T-cell-deficient mice and promote human T cell generation in NOD/SCID mice engrafted with human hematopoietic stem cells (hHSCs). These findings could facilitate hESC-based replacement therapy and provide a valuable in vitro platform for studying human thymus organogenesis and regeneration.

语种英语
所属项目编号2012CB966401 ; 2011ZX09102-010-03 ; 2012ZX10001-008 ; 2013ZX10001003 ; 2011DFA30730 ; 2013DFG30680 ; 37871 ; 30900855 ; 20080440269
资助者National Basic Research Program of China (973 program) ; Key New Drug Creation and Manufacturing Program ; National Science and Technology Major Project ; Ministry of Science and Technology ; 111 project ; Bill &amp ; Melinda Gates Foundation ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation ; National Basic Research Program of China (973 program) ; Key New Drug Creation and Manufacturing Program ; National Science and Technology Major Project ; Ministry of Science and Technology ; 111 project ; Bill &amp ; Melinda Gates Foundation ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation
WOS记录号WOS:000329570600015
引用统计
被引频次:36[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/124011
专题北京大学医药卫生分析中心
作者单位1.Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Key Lab Chem Genom, Shenzhen 518055, Peoples R China
2.Peking Univ, Coll Life Sci, Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China
3.Peking Univ, Ctr Life Sci, Beijing 100871, Peoples R China
4.Peking Univ, Ctr Med & Hlth Anal, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Sun, Xiaoning,Xu, Jun,Lu, Hongxia,et al. Directed Differentiation of Human Embryonic Stem Cells into Thymic Epithelial Progenitor-like Cells Reconstitutes the Thymic Microenvironment In Vivo[J]. CELL STEM CELL,2013,13(2):230-236.
APA Sun, Xiaoning.,Xu, Jun.,Lu, Hongxia.,Liu, Wang.,Miao, Zhenchuan.,...&Deng, Hongkui.(2013).Directed Differentiation of Human Embryonic Stem Cells into Thymic Epithelial Progenitor-like Cells Reconstitutes the Thymic Microenvironment In Vivo.CELL STEM CELL,13(2),230-236.
MLA Sun, Xiaoning,et al."Directed Differentiation of Human Embryonic Stem Cells into Thymic Epithelial Progenitor-like Cells Reconstitutes the Thymic Microenvironment In Vivo".CELL STEM CELL 13.2(2013):230-236.
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