Universität zu Köln

O'Neill, Kathy E., Bredenkamp, Nicholas, Tischner, Christin, Vaidya, Harsh J., Stenhouse, Frances H., Peddie, C. Diana, Nowell, Craig S., Gaskell, Terri and Blackburn, C. Clare (2016). Foxn1 Is Dynamically Regulated in Thymic Epithelial Cells during Embryogenesis and at the Onset of Thymic Involution. PLoS One, 11 (3). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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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, Foxn1(G), 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code O'Neill, Kathy E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bredenkamp, Nicholas UNSPECIFIED UNSPECIFIED UNSPECIFIED Tischner, Christin UNSPECIFIED UNSPECIFIED UNSPECIFIED Vaidya, Harsh J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stenhouse, Frances H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peddie, C. Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Nowell, Craig S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaskell, Terri UNSPECIFIED UNSPECIFIED UNSPECIFIED Blackburn, C. Clare UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-281244
DOI:	10.1371/journal.pone.0151666
Journal or Publication Title:	PLoS One
Volume:	11
Number:	3
Date:	2016
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FUNCTIONAL THYMUS; PROGENITOR-CELL; ADULT THYMUS; STEM-CELLS; MOUSE; NUDE; EXPRESSION; MICROENVIRONMENT; DIFFERENTIATION; THYMOPOIESIS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28124