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Committing Embryonic Stem Cells to Differentiate into Thyrocyte-Like Cells in Vitro

Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine (R.-Y.L., T.F.D.) and Carl C. Icahn Institute for Gene Therapy and Molecular Medicine (A.K., G.M.K.), Mount Sinai School of Medicine, New York, New York 10029

Address all correspondence and requests for reprints to: Reigh-Yi Lin, Ph.D., Department of Medicine, Mount Sinai School of Medicine, Box 1055, One Gustave L. Levy Place, New York, New York 10029-6574. E-mail: reigh-yi.lin{at}mssm.edu.

The derivation of thyrocyte-like cells in culture is of importance in the basic study of early thyroid embryogenesis and the generation of an unlimited clinical source of thyrocytes for genetic manipulation and cell transplantation. We have established an experimental system, which shows that 6-d-old embryoid bodies (EBs) differentiated from mouse embryonic stem (ES) cells expressed a set of genes traditionally associated with thyroid cells. The genes analyzed included the thyroid transcription factor PAX8, the Na⁺/I^- symporter, thyroperoxidase, thyroglobulin, and the TSH receptor (TSHR). Immunofluorescent analysis demonstrated the presence of TSHR-positive cells as outgrowths from 8-d-old EBs cultured on chamber slides. Accordingly, this area of cells also expressed PAX8 and another thyroid transcription factor TTF2. Of importance, TSH, the main regulator of the thyroid gland, was necessary to maintain the expression of PAX8 and TSHR genes during EB differentiation. Furthermore, thyroid-specific function, such as cAMP generation by TSH, was maintained in this model. Together, these results suggested that the developmental program associated with thyrocyte development is recapitulated in the ES/EB model system. The differentiation of mouse ES cells into thyrocyte-like cells provides a powerful model for the study of thyrocyte developmental diseases associated with this lineage and contributes to the development of thyroid hormone-secreting cell lines.

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