Development of a functional thyroid model based on an organoid culture system

Yoshiyuki Saito; Nobuyuki Onishi; Hiroshi Takami; Ryo Seishima; Hiroyoshi Inoue; Yuki Hirata; Kaori Kameyama; Kenji Tsuchihashi; Eiji Sugihara; Shinya Uchino; Koichi Ito; Hirofumi Kawakubo; Hiroya Takeuchi; Yuko Kitagawa; Hideyuki Saya; Osamu Nagano

doi:10.1016/j.bbrc.2018.02.154

Development of a functional thyroid model based on an organoid culture system

Yoshiyuki Saito, Nobuyuki Onishi, Hiroshi Takami, Ryo Seishima, Hiroyoshi Inoue, Yuki Hirata, Kaori Kameyama, Kenji Tsuchihashi, Eiji Sugihara, Shinya Uchino, Koichi Ito, Hirofumi Kawakubo, Hiroya Takeuchi, Yuko Kitagawa, Hideyuki Saya, Osamu Nagano

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

Abstract

The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid–like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRAS^Q61R) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer.

Original language	English
Pages (from-to)	783-789
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	497
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2018.02.154
Publication status	Published - Mar 4 2018
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2018.02.154

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Saito, Y., Onishi, N., Takami, H., Seishima, R., Inoue, H., Hirata, Y., Kameyama, K., Tsuchihashi, K., Sugihara, E., Uchino, S., Ito, K., Kawakubo, H., Takeuchi, H., Kitagawa, Y., Saya, H., & Nagano, O. (2018). Development of a functional thyroid model based on an organoid culture system. Biochemical and Biophysical Research Communications, 497(2), 783-789. https://doi.org/10.1016/j.bbrc.2018.02.154

Saito, Y, Onishi, N, Takami, H, Seishima, R, Inoue, H, Hirata, Y, Kameyama, K, Tsuchihashi, K, Sugihara, E, Uchino, S, Ito, K, Kawakubo, H, Takeuchi, H, Kitagawa, Y, Saya, H & Nagano, O 2018, 'Development of a functional thyroid model based on an organoid culture system', Biochemical and Biophysical Research Communications, vol. 497, no. 2, pp. 783-789. https://doi.org/10.1016/j.bbrc.2018.02.154

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abstract = "The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid–like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRASQ61R) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer.",

author = "Yoshiyuki Saito and Nobuyuki Onishi and Hiroshi Takami and Ryo Seishima and Hiroyoshi Inoue and Yuki Hirata and Kaori Kameyama and Kenji Tsuchihashi and Eiji Sugihara and Shinya Uchino and Koichi Ito and Hirofumi Kawakubo and Hiroya Takeuchi and Yuko Kitagawa and Hideyuki Saya and Osamu Nagano",

note = "Funding Information: This work was supported by Japan Society for the Promotion of Science KAKENHI grant 17H02583 (to O.N.). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

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doi = "10.1016/j.bbrc.2018.02.154",

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AU - Saito, Yoshiyuki

AU - Onishi, Nobuyuki

AU - Takami, Hiroshi

AU - Seishima, Ryo

AU - Inoue, Hiroyoshi

AU - Hirata, Yuki

AU - Kameyama, Kaori

AU - Tsuchihashi, Kenji

AU - Sugihara, Eiji

AU - Uchino, Shinya

AU - Ito, Koichi

AU - Kawakubo, Hirofumi

AU - Takeuchi, Hiroya

AU - Kitagawa, Yuko

AU - Saya, Hideyuki

AU - Nagano, Osamu

PY - 2018/3/4

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N2 - The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid–like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRASQ61R) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer.

AB - The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid–like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRASQ61R) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer.

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Development of a functional thyroid model based on an organoid culture system

Abstract

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