title: Directed differentiation of human embryonic stem cells into thymic epithelial progenitor-like cells reconstitutes the thymic microenvironment in vivo.
abstract: 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 support mouse 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.
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Lu
authors.forename: Wang
authors.initials: W
authors.lastname: Liu
authors.forename: Zhenchuan
authors.initials: Z
authors.lastname: Miao
authors.forename: Xin
authors.initials: X
authors.lastname: Sui
authors.forename: Haisong
authors.initials: H
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: Weichao
authors.initials: W
authors.lastname: Du
authors.forename: Qihua
authors.initials: Q
authors.lastname: He
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Hongkui
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D060833:Cellular Microenvironment; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004707:Endoderm / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D004848:Epithelium / Q000254:growth & development; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology