Abstract

We have identified side population (SP) cells in the adult mouse thyroid. SP cells are characterized by their ability to efflux the vital dye Hoechst 33342 when analyzed by flow cytometry, due to expression of the ATP binding cassette (ABC)-dependent transporter ABCG2, and are highly enriched for stem/progenitor cell activity. Thyroid SP cells highly express ABCG2 and the stem cell marker genes encoding nucleostemin and Oct4, whereas the expression of genes encoding the thyroid differentiation markers such as thyroid peroxidase, thyroglobulin, and TSH receptor, and two transcription factors, T/EBP and PAX8, critical for thyroid specific gene expression, are low in the SP fraction of cells as examined by RT- and real-time PCR. These results suggest that adult thyroid may contain stem/progenitor cells. Our current focus is to identify another cell surface marker that can be used in conjunction with SP fraction to further enrich thyroid stem/progenitor-like cells. As one of proof that they are the genuine stem/progenitor cells of thyroid, we culture these cells in culture dish and/or collagen gel three dimensional system, to induce thyroid-specific gene expression and/or thyroid cell-like morphology.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005522-19
Application #
7337867
Study Section
(BLM)
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
2006
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Hoshi, Sayuri; Hoshi, Nobuo; Okamoto, Minoru et al. (2009) Role of NKX2-1 in N-bis(2-hydroxypropyl)-nitrosamine-induced thyroid adenoma in mice. Carcinogenesis 30:1614-9
Hoshi, Nobuo; Kusakabe, Takashi; Taylor, Barbara J et al. (2007) Side population cells in the mouse thyroid exhibit stem/progenitor cell-like characteristics. Endocrinology 148:4251-8
Zhang, Yuzhen; Rath, Nibedita; Hannenhalli, Sridhar et al. (2007) GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo. Development 134:189-98
Yeager, Nicole; Klein-Szanto, Andres; Kimura, Shioko et al. (2007) Pten loss in the mouse thyroid causes goiter and follicular adenomas: insights into thyroid function and Cowden disease pathogenesis. Cancer Res 67:959-66
Yin, Zhan; Gonzales, Linda; Kolla, Venkatadri et al. (2006) Hop functions downstream of Nkx2.1 and GATA6 to mediate HDAC-dependent negative regulation of pulmonary gene expression. Am J Physiol Lung Cell Mol Physiol 291:L191-9
Kusakabe, Takashi; Hoshi, Nobuo; Kimura, Shioko (2006) Origin of the ultimobranchial body cyst: T/ebp/Nkx2.1 expression is required for development and fusion of the ultimobranchial body to the thyroid. Dev Dyn 235:1300-9
Niimi, Tomoaki; Kurotani, Reiko; Kimura, Shioko et al. (2006) Identification and expression of alternative splice variants of the mouse Ppp1r3b gene in lung epithelial cells. Biochem Biophys Res Commun 349:588-96
Kusakabe, Takashi; Kawaguchi, Akio; Hoshi, Nobuo et al. (2006) Thyroid-specific enhancer-binding protein/NKX2.1 is required for the maintenance of ordered architecture and function of the differentiated thyroid. Mol Endocrinol 20:1796-809
Amendola, Elena; De Luca, Pasquale; Macchia, Paolo Emidio et al. (2005) A mouse model demonstrates a multigenic origin of congenital hypothyroidism. Endocrinology 146:5038-47
Shima, Yuichi; Zubair, Mohamad; Ishihara, Satoru et al. (2005) Ventromedial hypothalamic nucleus-specific enhancer of Ad4BP/SF-1 gene. Mol Endocrinol 19:2812-23

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