title: An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts.
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.
authors.affiliation: 1] Medical Research Council Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh EH16 4UU, UK [2].
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bredenkamp
authors.affiliation: Medical Research Council Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ulyanchenko
authors.affiliation: Medical Research Council Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Kathy Emma
authors.initials: KE
authors.lastname: O'Neill
authors.affiliation: Department of Genetics, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Nancy Ruth
authors.initials: NR
authors.lastname: Manley
authors.affiliation: Medical Research Council Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Harsh Jayesh
authors.initials: HJ
authors.lastname: Vaidya
authors.affiliation: Medical Research Council Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Catherine Clare
authors.initials: CC
authors.lastname: Blackburn
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology / Q000637:transplantation; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D044968:Regenerative Medicine; D013601:T-Lymphocytes / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein