title: Dynamic spatio-temporal contribution of single β5t+ cortical epithelial precursors to the thymus medulla.
abstract: Intrathymic T-cell development is critically dependent on cortical and medullary thymic epithelial cells (TECs). Both epithelial subsets originate during early thymus organogenesis from progenitor cells that express the thymoproteasome subunit β5t, a typical feature of cortical TECs. Using in vivo lineage fate mapping, we demonstrate in mice that β5t(+) TEC progenitors give rise to the medullary TEC compartment early in life but significantly limit their contribution once the medulla has completely formed. Lineage-tracing studies at single cell resolution demonstrate for young mice that the postnatal medulla is expanded from individual β5t(+) cortical progenitors located at the cortico-medullary junction. These results therefore not only define a developmental window during which the expansion of medulla is efficiently enabled by progenitors resident in the thymic cortex, but also reveal the spatio-temporal dynamics that control the growth of the thymic medulla.
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Mayer
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Saulius
authors.initials: S
authors.lastname: Žuklys
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Saule
authors.initials: S
authors.lastname: Zhanybekova
authors.affiliation: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Ohigashi
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Teh
authors.affiliation: The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Sansom
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Noriko
authors.initials: N
authors.lastname: Shikama-Dorn
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hafen
authors.affiliation: Wellcome Trust Sanger Institute-EBI Single Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macaulay
authors.affiliation: Department of Paediatrics and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Deadman
authors.affiliation: Wellcome Trust Sanger Institute-EBI Single Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.|MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors.forename: Chris P
authors.initials: CP
authors.lastname: Ponting
authors.affiliation: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.|Department of Paediatrics and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Holländer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation; D004318:Doxycycline / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038081:Organogenesis / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology*
chemical_list: D046988:Proteasome Endopeptidase Complex; C520309:proteasome subunit beta5t, mouse; D004318:Doxycycline
keywords: Development; Epithelial cell; Medulla; Thymic progenitor cell; β5t