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An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts.

TitleAn organized and functional thymus generated from FOXN1-reprogrammed fibroblasts.
Publication TypeJournal Article
Year of Publication2014
AuthorsBredenkamp N, Ulyanchenko S, O'Neill KE, Manley NRuth, Vaidya HJayesh, C Blackburn C
JournalNat Cell Biol
Volume16
Issue9
Pagination902-8
Date Published2014 Sep
ISSN1476-4679
Abstract

A central goal of regenerative medicine is to generate transplantable organs from cells derived or expanded in vitro. Although numerous studies have demonstrated the production of defined cell types in vitro, the creation of a fully intact organ has not been reported. The transcription factor forkhead box N1 (FOXN1) is critically required for development of thymic epithelial cells (TECs), a key cell type of the thymic stroma. Here, we show that enforced Foxn1 expression is sufficient to reprogramme fibroblasts into functional TECs, an unrelated cell type across a germ-layer boundary. These FOXN1-induced TECs (iTECs) supported efficient development of both CD4(+) and CD8(+) T cells in vitro. On transplantation, iTECs established a complete, fully organized and functional thymus, that contained all of the TEC subtypes required to support T-cell differentiation and populated the recipient immune system with T cells. iTECs thus demonstrate that cellular reprogramming approaches can be used to generate an entire organ, and open the possibility of widespread use of thymus transplantation to boost immune function in patients.

DOI10.1038/ncb3023
Alternate JournalNat. Cell Biol.
PubMed ID25150981
PubMed Central IDPMC4153409
Grant ListG0300058 / / Medical Research Council / United Kingdom
MR/K017047/1 / / Medical Research Council / United Kingdom
R01 AI082127 / AI / NIAID NIH HHS / United States
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