title: Foxn1 Is Dynamically Regulated in Thymic Epithelial Cells during Embryogenesis and at the Onset of Thymic Involution.
abstract: Thymus function requires extensive cross-talk between developing T-cells and the thymic epithelium, which consists of cortical and medullary TEC. The transcription factor FOXN1 is the master regulator of TEC differentiation and function, and declining Foxn1 expression with age results in stereotypical thymic involution. Understanding of the dynamics of Foxn1 expression is, however, limited by a lack of single cell resolution data. We have generated a novel reporter of Foxn1 expression, Foxn1G, to monitor changes in Foxn1 expression during embryogenesis and involution. Our data reveal that early differentiation and maturation of cortical and medullary TEC coincides with precise sub-lineage-specific regulation of Foxn1 expression levels. We further show that initiation of thymic involution is associated with reduced cTEC functionality, and proportional expansion of FOXN1-negative TEC in both cortical and medullary sub-lineages. Cortex-specific down-regulation of Foxn1 between 1 and 3 months of age may therefore be a key driver of the early stages of age-related thymic involution.
authors.affiliation: MRC 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 E
authors.initials: KE
authors.lastname: O'Neill
authors.affiliation: MRC 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: Nicholas
authors.initials: N
authors.lastname: Bredenkamp
authors.affiliation: MRC 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: Christin
authors.initials: C
authors.lastname: Tischner
authors.affiliation: MRC 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 J
authors.initials: HJ
authors.lastname: Vaidya
authors.affiliation: MRC 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: Frances H
authors.initials: FH
authors.lastname: Stenhouse
authors.affiliation: MRC 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: C Diana
authors.initials: CD
authors.lastname: Peddie
authors.affiliation: MRC 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: Craig S
authors.initials: CS
authors.lastname: Nowell
authors.affiliation: MRC 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: Terri
authors.initials: T
authors.lastname: Gaskell
authors.affiliation: MRC 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: C Clare
authors.initials: CC
authors.lastname: Blackburn
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D015536:Down-Regulation; D047108:Embryonic Development / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D013950:Thymus Gland / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein