TY - JOUR
T1 - Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism
AU - van der Vaart, Jelte
AU - Bosmans, Lynn
AU - Sijbesma, Stijn F.
AU - Knoops, Kevin
AU - van de Wetering, Willine J.
AU - Otten, Henny G.
AU - Begthel, Harry
AU - Borel Rinkes, Inne H.M.
AU - Korving, Jeroen
AU - Lentjes, Eef G.W.M.
AU - Lopez-Iglesias, Carmen
AU - Peters, Peter J.
AU - van Santen, Hanneke M.
AU - Vriens, Menno R.
AU - Clevers, Hans
N1 - Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.
PY - 2021/12/21
Y1 - 2021/12/21
N2 - 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.
AB - 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.
KW - Graves’ disease
KW - Organoids
KW - Thyroid
UR - http://www.scopus.com/inward/record.url?scp=85122632093&partnerID=8YFLogxK
U2 - 10.1073/pnas.2117017118
DO - 10.1073/pnas.2117017118
M3 - Article
C2 - 34916298
AN - SCOPUS:85122632093
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 51
M1 - e2117017118
ER -