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Lessons from Thymic Epithelial Heterogeneity: FoxN1 and Tissue-Restricted Gene Expression by Extrathymic, Endodermally Derived Epithelium¹

James Dooley,^* Matthew Erickson,^* and Andrew G. Farr^2*

^*Department of Biological Structure, Department of Immunology, and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195

Modeling of thymic epithelial differentiation has been guided by several important underlying assumptions. One is that within epithelial tissues derived from pharyngeal endoderm, FoxN1 expression is signature for the thymic epithelial lineage. Another is that expression of tissue-restricted Ag (TRA) is a unique feature of thymic epithelium. In this murine study, we evaluate the thymic expression of a subset of TRA, parathyroid hormone, calcitonin, and thyroglobulin, as part of an effort to better define the heterogeneity of medullary thymic epithelial cells. In this study, we demonstrate that both conventional and cystic epithelial cells display a history of FoxN1 expression using a cre-lox approach. We also document that extrathymic epithelial tissues that originate from pharyngeal endoderm also have a history of FoxN1 expression, indicating that FoxN1 expression per se is not a signature for the thymic lineage and suggesting that FoxN1 expression, whereas necessary for thymic epithelium, development, is not sufficient for this process to occur. Both cystic and conventional medullary thymic epithelial cells express these TRAs, as do extrathymic epithelial tissues that are not usually considered to be sources of these molecules. This finding supports the proposition that promiscuous gene expression is not unique to the thymus. Furthermore, the pattern of promiscuous gene expression in these extrathymic epithelia is consistent with developmental regulation processes and suggests that it is premature to discard the possibility that some promiscuous gene expression in the thymus reflects normal differentiation programs of epithelia.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant AI09575 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases.

² Address correspondence and reprint requests to Dr. Andrew G. Farr, Department of Biological Structure, Box 357420, School of Medicine, University of Washington, Seattle, WA 98195-7420. E-mail address: farr{at}u.washington.edu

³ Abbreviations used in this paper: MTEC, medullary thymic epithelial cell; TRA, tissue-restricted Ag; Pth, parathyroid hormone; YFP, yellow fluorescent protein.

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The JI 2009 183: 4829-4830. [Full Text]