An organized and functional thymus generated from ​FOXN1-reprogrammed fibroblast

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http://www.nature.com/ncb/journal/v16/n9/full/ncb3023.html

An organized and functional thymus generated from ​FOXN1-reprogrammed fibroblasts
Nicholas Bredenkamp, Svetlana Ulyanchenko, Kathy Emma O’Neill, Nancy Ruth Manley, Harsh Jayesh Vaidya & Catherine Clare Blackburn
NATURE CELL BIOLOGY
Nature Cell Biology 16, 902–908 (2014) doi:10.1038/ncb3023

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 vitro1, 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 cells2, 3 (TECs), a key cell type of the thymic stroma4. 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.
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