RRC ID 50306
Author 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.
Title Development of a functional thyroid model based on an organoid culture system.
Journal Biochem Biophys Res Commun
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.
Volume 497(2)
Pages 783-789
Published 2018-3-4
DOI 10.1016/j.bbrc.2018.02.154
PII S0006-291X(18)30391-7
PMID 29470983
MeSH Animals Female GTP Phosphohydrolases / genetics Gene Expression Regulation, Neoplastic Humans Membrane Proteins / genetics Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, SCID Mice, Transgenic Organ Culture Techniques / methods* Organoids / cytology* Organoids / pathology Organoids / physiology Point Mutation Thyroid Gland / cytology* Thyroid Gland / pathology Thyroid Gland / physiology Thyroid Neoplasms / genetics Thyroid Neoplasms / pathology Tumor Suppressor Protein p53 / genetics
IF 2.985
Times Cited 6
Mice RBRC01361