Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves' hyperthyroidism

Jelte van der Vaart, Lynn Bosmans, Stijn F Sijbesma, Kèvin Knoops, Willine J van de Wetering, Henny G Otten, Harry Begthel, Inne H M Borel Rinkes, Jeroen Korving, Eef G W M Lentjes, Carmen Lopez-Iglesias, Peter J Peters, Hanneke M van Santen, Menno R Vriens, Hans Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number51
DOIs
Publication statusPublished - 21 Dec 2021

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