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, Yuukou Kitagawa, Hideyuki Saya, Osamu Nagano

Research output: Contribution to journalArticle

6 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 (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.

Original languageEnglish
Pages (from-to)783-789
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume497
Issue number2
DOIs
Publication statusPublished - 2018 Mar 4

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Keywords

  • NRAS
  • Organoid
  • p53
  • Thyroid
  • Thyroid cancer model

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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