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

Jelte van der Vaart; Lynn Bosmans; Stijn F. Sijbesma; Kevin 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

doi:10.1073/pnas.2117017118

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

Jelte van der Vaart, Lynn Bosmans, Stijn F. Sijbesma, Kevin 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

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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.

Originele taal-2	Engels
Artikelnummer	e2117017118
Tijdschrift	Proceedings of the National Academy of Sciences of the United States of America
Volume	118
Nummer van het tijdschrift	51
DOI's	https://doi.org/10.1073/pnas.2117017118
Status	Gepubliceerd - 21 dec. 2021

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10.1073/pnas.2117017118

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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. (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), Artikel e2117017118. https://doi.org/10.1073/pnas.2117017118

@article{05411fc3da484998937dd0377e2c7c6a,

title = "Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves{\textquoteright} hyperthyroidism",

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{\textquoteright} disease patient sera, demonstrating that organoids can model human autoimmune disease.",

keywords = "Graves{\textquoteright} disease, Organoids, Thyroid",

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

year = "2021",

month = dec,

day = "21",

doi = "10.1073/pnas.2117017118",

language = "English",

volume = "118",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "51",

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van der Vaart, J, Bosmans, L, Sijbesma, SF, Knoops, K, van de Wetering, WJ, Otten, HG, Begthel, H, Borel Rinkes, IHM, Korving, J, Lentjes, EGWM, Lopez-Iglesias, C, Peters, PJ, van Santen, HM, Vriens, MR & 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, vol. 118, nr. 51, e2117017118. https://doi.org/10.1073/pnas.2117017118

Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism. / van der Vaart, Jelte; Bosmans, Lynn; Sijbesma, Stijn F. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 118, Nr. 51, e2117017118, 21.12.2021.

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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

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

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U2 - 10.1073/pnas.2117017118

DO - 10.1073/pnas.2117017118

M3 - Article

C2 - 34916298

AN - SCOPUS:85122632093

SN - 0027-8424

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

IS - 51

M1 - e2117017118

ER -

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

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