Functional evidence for a single endodermal origin for the thymic epithelium

Abstract

T cell development depends critically on several distinct thymic epithelial cell types that are organized into two main compartments: cortex and medulla. The prevailing hypothesis suggests that these derive from ectoderm and endoderm, respectively. Here we show that lineage analysis provides no evidence for an ectodermal contribution to the thymic rudiment. We further demonstrate, via ectopic transplantation, that isolated pharyngeal endoderm can generate a functional thymus containing organized cortical and medullary regions and that this capacity is not potentiated by the presence of pharyngeal ectoderm. These data establish that the cortical and medullary thymic epithelial compartments derive from a single germ layer, the endoderm, thus refuting the 'dual-origin' model of thymic epithelial ontogeny.

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Figure 1: Histological and TUNEL analysis of early thymus organogenesis.
Figure 2: Fate of pharyngeal ectoderm lineage cells.
Figure 3: Potency of the pharyngeal endoderm.
Figure 4: Analysis of grafts recovered from endoderm-only recipients demonstrates the presence of cortical and medullary thymic epithelial cells.
Figure 5: Analysis of grafts recovered from endoderm-only recipients demonstrates the presence of differentiating thymocytes.
Figure 6: Endoderm-derived thymi can support thymocyte development.
Figure 7: Histological analysis of grafts recovered from whole-arch recipients.

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Acknowledgements

We thank A. Medvinsky for critical discussion, C.L. Bennett for assistance with flow cytometry and Biomed Unit staff for animal care. Supported by the Medical Research Council, UK (C.C.B., J.G., J.S. and V.A.W.), Leukaemia Research Fund, UK (C.C.B., N.B. and A.F.), National Institutes of Health-National Institute of Child Health and Human Development (HD035920 to N.R.M.) and Wellcome Trust (C.C.B. and N.R.M.).

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Correspondence to C Clare Blackburn.

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Gordon, J., Wilson, V., Blair, N. et al. Functional evidence for a single endodermal origin for the thymic epithelium. Nat Immunol 5, 546–553 (2004). https://doi.org/10.1038/ni1064

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