Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 40, Issue 2, Pages 530-538Publisher
WILEY
DOI: 10.1002/eji.200939605
Keywords
Aire; Epithelial cells; Spatial; Thymic ontogeny
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Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Provence-Alpes-Cote d'Azur region
- Association Francaise contre les Myopathies (AFM)
- Association pour la Recherche sur le Cancer (ARC)
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The Spatial gene is expressed in highly polarized cell types such as testis germ cells, brain neurons and thymic epithelial cells (TEC). Its expression was documented in testis and brain but poorly characterized in thymus. Here, we characterize for the first time Spatial-expressing TEC throughout ontogeny and adult mouse thymus. Spatial is expressed in thymicfated domain by embryonic day E10.5 and persists in subcapsular, cortical, medullary epithelial cells and in MTS24(+) progenitor TEC. Using mouse strains in which thymocyte development is blocked at various stages, we show that Spatial expression is independent of thymocyte-derived signals during thymus organogenesis. Analyses on purified thymic cell subsets show that Spatial short isoforms are expressed in cortical TEC (cTEC) and mature medullary TEC (mTEC). Spatial long isoforms were detected in the same TEC population. Spatial presents a nuclear distribution specific to mature mTEC expressing UEA1 and Aire. Aire- and RANKL-deficient mice revealed that Spatial expression is drastically reduced in the thymus of these mutants. These findings reveal a critical function of Aire in regulating Spatial expression, which is compatible with promiscuous Spatial gene expression.
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