Abstract
The thyroid gland is centrally important in metabolic homeostasis, growth, and development. Defects in any of the multiple steps required for normal thyroid development and thyroid hormone synthesis have been shown to result in thyroid-dependent pathology in a variety of animal models of disease and in humans. However, there are many unanswered questions regarding the cellular and molecular mechanisms leading to thyrocyte abnormalities. A lack of knowledge regarding thyroid stem/progenitor cell differentiation and proliferation has further hampered attempts to gain more insight into thyroid-associated disease mechanisms. In this chapter, we present a culture system that has successfully generated thyrocyte-like cells from undifferentiated embryonic stem cells in vitro. Access to specific early-developing cell populations, such as the thyroid stem cells in the embryonic stem cell system, provides an experimental approach to characterizing key molecular events involved in thyrocyte commitment.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Davies T. F., Yang C., and Platzer M. (1987) Cloning of the Fisher rat thyroid cell line (FRTL-5): variability in clonal growth and cyclic AMP response to thyrotropin. Endocrinology 121, 78–83.
Davies T. F., Platzer M., Schwartz A. E., and Friedman E. W. (1985) Short-and long-term evaluation of normal and abnormal human thyroid cells in monolayer culture. Clin. Endocrinol. (Oxford) 23, 469–479.
Huber G. K. and Davies T. F. (1990) Human fetal thyroid cell growth in vitro: system characterization and cytokine inhibition. Endocrinology 126, 869–875.
Ambesi-Impiombato F. S. and Coon H. G. (1979) Thyroid cells in culture. Int. Rev. Cytol. Suppl. 10, 163–172.
Curcio F., Ambesi-Impiombato F. S., Perrella G., and Coon H.G. (1994) Long-term culture and functional characterization of follicular cells from adult normal human thyroids. Proc. Natl. Acad. Sci. USA 91, 9004–9008.
Fayet G. and Hovsepian S. (2002) Isolation of a normal human thyroid cell line: hormonal requirement for thyroglobulin regulation. Thyroid 12, 539–546.
Weiss S. J., Philp N. J., and Grollman E. F. (1984) Effect of thyrotropin on iodide efflux in FRTL-5 cells mediated by Ca2+. Endocrinology 114, 1108–1113.
Fusco A., Berlingieri M. T., Di Fiore P. P., Portella G., Grieco M., and Vecchio G. (1987) One-and two-step transformations of rat thyroid epithelial cells by retroviral oncogenes. Mol. Cell Biol. 7, 3365–3370.
Ambesi-Impiombato F. S., Parks L. A. M., and Coon H. G. (1980) Culture of hormonedependent functional epithelial cells from rat thyroids. Proc. Natl. Acad. Sci. USA 77, 3455–3459.
Tasevski V., Benn D., Peters G., Luttrell B., and Simpson A. (1998) The Fischer rat thyroid cell line FRTL-5 exhibits a nondiploid karyotype. Thyroid 8, 623–626.
Zimmermann-Belsing T., Rasmussen A. K., and Feldt-Rasmussen U. (1998) Lack of thyroglobulin synthesis as an indicator of early random dedifferentiation of the Fischer rat thyroid cell line FRTL-5. Scand. J. Clin. Lab. Invest. 58, 529–535.
Evans M. J. and Kaufman M. H. (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154–156.
Martin G. R. (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. USA 78, 7634–7638.
Keller G. M. (1995) In vitro differentiation of embryonic stem cells. Curr. Opin. Cell Biol. 7, 862–869.
Doetschman T., Shull M., Kier A., and Coffin J. D. (1993) Embryonic stem cell model systems for vascular morphogenesis and cardiac disorders. Hypertension 22, 618–629.
Keller G., Kennedy M., Papayannopoulou T., and Wiles M. V. (1993) Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol. Cell Biol. 13, 473–486.
Bain G., Kitchens D., Yao M., Huettner J. E., and Gottlieb D. I. (1995) Embryonic stem cells express neuronal properties in vitro. Dev. Biol. 168, 342–357.
Kawasaki H., Mizuseki K., Nishikawa S., et al. (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28, 31–40.
Brustle O., Jones K. N., Learish R. D., et al. (1999) Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285, 754–756.
Lumelsky N., Blondel O., Laeng P., Velasco I., Ravin R., and McKay R. (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292, 1389–1394.
Soria B., Roche E., Berna G., Leon-Quinto T., Reig J. A., and Martin F. (2000) Insulinsecreting cells derived from embryonic stem cells normalize glycemia in streptozotocininduced diabetic mice. Diabetes 49, 157–162.
Chinzei R., Tanaka Y., Shimizu-Saito K., et al. (2002) Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes. Hepatology 36, 22–29.
Boheler K. R., Czyz J., Tweedie D., Yang H. T., Anisimov S. V., and Wobus A. M. (2002) Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ. Res. 91, 189–201.
Civitareale D., Castelli M. P., Falasca P., and Saiardi A. (1993) Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene. Mol. Endocrinol. 7, 1589–1595.
Miccadei S., De Leo R., Zammarchi E., Natali P. G., and Civitareale. (2002) The synergistic activity of thyroid transcription factor 1 and pax 8 relies on the promoter/enhancer interplay. Mol. Endocrinol. 16, 837–846.
Mansouri A., Chowdhury K., and Gruss P. (1998) Follicular cells of the thyroid gland require Pax8 gene function. Nat. Genet. 19, 87–90.
Damante G., Tell G., and Di Lauro R. (2001) A unique combination of transcription factors controls differentiation of thyroid cells. Prog. Nucleic Acid Res. Mol. Biol. 66, 307–356.
Dai G., Levy O., and Carrasco N. (1996) Cloning and characterization of the thyroid iodide transporter. Nature 379, 458–460.
Weiss S. J., Philp N. J., Ambesi-Impiombato F. S., and Grollman E. F. (1984) Thyrotropinstimulated iodide transport mediated by adenosine 3′,5′-monophosphate and dependent on protein synthesis. Endocrinology 114, 1099–1107.
Davies T., Marians R., and Latif R. (2002) The TSH receptor reveals itself. J. Clin. Invest. 110, 161–164.
Lin R. Y., Kubo A., Keller G. M., and Davies T. F. (2003) Committing embryonic stem cells to differentiate into thyrocyte-like cells in vitro. Endocrinology 144, 2644–2649.
Robertson E., Bradley A., Kuehn M., and Evans M. (1986) Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature 323, 445–448.
Kubo A., Shinozaki K., Shannon J. M., et al. (2004) Development of definitive endoderm from embryonic stem cells in culture. Development 131, 1651–1662.
Parmentier M., Libert F., Maenhaut C., et al. (1989) Molecular cloning of the thyrotropin receptor. Science 246, 1620–1622.
Van Heuverswyn B., Leriche A., Van Sande J., Dumont J. E., and Vassart G. (1985) Transcriptional control of thyroglobulin gene expression by cyclic AMP. FEBS Lett. 188, 192–196.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Humana Press Inc.
About this protocol
Cite this protocol
Lin, RY., Davies, T.F. (2006). Derivation and Characterization of Thyrocyte-Like Cells From Embryonic Stem Cells In Vitro. In: Turksen, K. (eds) Embryonic Stem Cell Protocols. Methods in Molecular Biology™, vol 330. Humana Press. https://doi.org/10.1385/1-59745-036-7:249
Download citation
DOI: https://doi.org/10.1385/1-59745-036-7:249
Publisher Name: Humana Press
Print ISBN: 978-1-58829-784-6
Online ISBN: 978-1-59745-036-2
eBook Packages: Springer Protocols