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Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium

Abstract

The thymus provides an essential environment for the development of T cells from haemopoietic progenitors. This environment is separated into cortical and medullary regions, each containing functionally distinct epithelial populations that are important at successive stages of T-cell development and selection1,2. However, the developmental origin and lineage relationships between cortical and medullary epithelial cell types remain controversial3. Here we describe a clonal assay to investigate the developmental potential of single, individually selected, thymic epithelial progenitors (marked with enhanced yellow fluorescent protein) developing within the normal architecture of the thymus. Using this approach, we show that cortical and medullary epithelial cells share a common origin in bipotent precursors, providing definitive evidence that they have a single rather than dual germ layer origin during embryogenesis. Our findings resolve a long-standing issue in thymus development, and are important in relation to the development of cell-based strategies for thymus disorders and the possibility of restoring function of the atrophied adult thymus.

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Figure 1: A clonal assay for thymic epithelial progenitors.
Figure 2: A single E12 thymic epithelial cell gives rise to multiple progeny in both cortical and medullary locations in vivo.
Figure 3: Analysis of progeny of single thymic epithelial cells using cortical epithelial markers.
Figure 4: Analysis of progeny of single thymic epithelial cells using medullary epithelial markers.

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Acknowledgements

We thank R. Bird for cell sorting, and S. Parnell and T. Jones for technical assistance. This work was supported by the European Union (FP6 Eurothymaide Constortium) and the Medical Research Council, UK. Author Contributions S.W.R. performed the experiments shown in Figs 23,4, S.W.R. and W.E.J. performed those shown in Fig. 1. G.A. and E.J.J. designed the experiments and wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Graham Anderson.

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Rossi, S., Jenkinson, W., Anderson, G. et al. Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium. Nature 441, 988–991 (2006). https://doi.org/10.1038/nature04813

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