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DOI	10.1073/pnas.2117017118
	Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism
	van der Vaart J.; Bosmans L.; Sijbesma S.F.; Knoops K.; van de Wetering W.J.; Otten H.G.; Begthel H.; Borel Rinkes I.H.M.; Korving J.; Lentjes E.G.W.M.; Lopez-Iglesias C.; Peters P.J.; van Santen H.M.; Vriens M.R.; Clevers H.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:51
英文摘要	The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of three-dimensional (3D) organoids from adult thyroid tissue representing murine and human thyroid follicular cells (TFCs). The TFC organoids (TFCOs) harbor the complete machinery of hormone production as visualized by the presence of colloid in the lumen and by the presence of essential transporters and enzymes in the polarized epithelial cells that surround a central lumen. Both the established murine as human thyroid organoids express canonical thyroid markers PAX8 and NKX2.1, while the thyroid hormone precursor thyroglobulin is expressed at comparable levels to tissue. Single-cell RNA sequencing and transmission electron microscopy confirm that TFCOs phenocopy primary thyroid tissue. Thyroid hormones are readily detectable in conditioned medium of human TFCOs. We show clinically relevant responses (increased proliferation and hormone secretion) of human TFCOs toward a panel of Graves’ disease patient sera, demonstrating that organoids can model human autoimmune disease. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Graves’ disease; Organoids; Thyroid
语种	英语
scopus关键词	homeobox protein Nkx 2.1; NKX2-1 protein, human; Nkx2-1 protein, mouse; PAX8 protein, human; Pax8 protein, mouse; thyroglobulin; transcription factor PAX8; animal; culture medium; gene expression regulation; genetics; Graves disease; human; metabolism; mouse; organoid; physiology; thyroid follicular cell; Animals; Culture Media; Gene Expression Regulation; Graves Disease; Humans; Mice; Organoids; PAX8 Transcription Factor; Thyroglobulin; Thyroid Epithelial Cells; Thyroid Nuclear Factor 1
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250909
作者单位	Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Centre Utrecht, Utrecht, 3584 CT, Netherlands; Oncode Institute, Utrecht, 3584 CT, Netherlands; Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, 6229 ER, Netherlands; Central Diagnostic Laboratory, Centre of Translational Immunology, University Medical Center (UMC) Utrecht, Utrecht, 3584 CX, Netherlands; Department of Surgical Oncology, UMC Utrecht Cancer Center, Utrecht, 3584 CX, Netherlands; Central Diagnostic Laboratory, University Medical Centre Utrecht, Utrecht, 3584 CX, Netherlands; Princess Maxima Center for Paediatric Oncology, Utrecht, 3584 CS, Netherlands; Department of Paediatric Endocrinology, Wilhelmina Children Hospital, University Medical Center Utrecht, Utrecht, 3584 EA, Netherlands
推荐引用方式 GB/T 7714	van der Vaart J.,Bosmans L.,Sijbesma S.F.,等. Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism[J],2021,118(51).
APA	van der Vaart J..,Bosmans L..,Sijbesma S.F..,Knoops K..,van de Wetering W.J..,...&Clevers H..(2021).Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism.Proceedings of the National Academy of Sciences of the United States of America,118(51).
MLA	van der Vaart J.,et al."Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism".Proceedings of the National Academy of Sciences of the United States of America 118.51(2021).