Journal
PLOS ONE
Volume 11, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0151666
Keywords
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Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/H021183/1BBSRC]
- Leukaemia and Lymphoma Research grant [12012]
- School of Biological Sciences, University of Edinburgh
- Medical Research Council [71380]
- European Union
- EuroSyStem
- ThymiStem [223098, 200720, 602587]
- BBSRC [BB/H021183/1] Funding Source: UKRI
- MRC [MR/L012766/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/H021183/1] Funding Source: researchfish
- Medical Research Council [MR/L012766/1] Funding Source: researchfish
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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.
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