The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
Generation of functional thyroid from embryonic stem cells
Open accessAbstract
The primary function of the thyroid gland is to metabolize iodide by synthesizing thyroid hormones, which are critical regulators of growth, development and metabolism in almost all tissues. So far, research on thyroid morphogenesis has been missing an efficient stem-cell model system that allows for the in vitro recapitulation of the molecular and morphogenic events regulating thyroid follicular-cell differentiation and subsequent assembly into functional thyroid follicles. Here we report that a transient overexpression of the transcription factors NKX2-1 and PAX8 is sufficient to direct mouse embryonic stem-cell differentiation into thyroid follicular cells that organize into three-dimensional follicular structures when treated with thyrotropin. These in vitro-derived follicles showed appreciable iodide organification activity. Importantly, when grafted in vivo into athyroid mice, these follicles rescued thyroid hormone plasma levels and promoted subsequent symptomatic recovery. Thus, mouse embryonic stem cells can be induced to differentiate into thyroid follicular cells in vitro and generate functional thyroid tissue.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The subsequent overexpression of the transcription factors NKX2.1 and PAX8 (67) led to fully differentiated follicular cells that express thyroid-specific genes such as TSH receptor, sodium/iodide symporter, and thyroglobulin.”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [67]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Exposure to human TSH causes these cells to organize in a 3D follicular architecture that was grafted under the kidney capsules of hypothyroid mice.”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [67]
The cited source says what the claim attributes to it.
In the citing paper
“Four weeks later, T4 levels became detectable and serum TSH levels were reduced when compared to levels before grafting (67).”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [67]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
Establishment in culture of pluripotential cells from mouse embryos
Evans, M. J., & Kaufman, M. H. (1981) · Nature · doi:10.1038/292154a0 · Cited by 8,623
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Martin, G. R. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.12.7634 · Cited by 5,756
Disease-Specific Induced Pluripotent Stem Cells.
Park, I.-H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M. W., Cowan, C., Hochedlinger, K., & Daley, G. Q. (2008) · Cell · doi:10.1016/j.cell.2008.07.041 · Cited by 2,196
Self-organizing optic-cup morphogenesis in three-dimensional culture
Eiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T., & Sasai, Y. (2011) · Nature · doi:10.1038/nature09941 · Cited by 2,001
Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells
D’Amour, K. A., Bang, A. G., Eliazer, S., Kelly, O., Agulnick, A. D., Smart, N. G., Moorman, M. A., KROON, E. J., Carpenter, M. K., & Baetge, E. E. (2006) · Nature Biotechnology · doi:10.1038/nbt1259 · Cited by 1,913
Directed differentiation of embryonic stem cells into motor neurons.
Wichterle, H., Lieberam, I., Porter, J. A., & Jessell, T. (2002) · Cell · doi:10.1016/s0092-8674(02)00835-8 · Cited by 1,792
Murry, C. E., & Keller, G. M. (2008) · Cell · doi:10.1016/j.cell.2008.02.008 · Cited by 1,760
Cited by
Sorted by citations
Items 301–360 of 360
Molecular characterisation of benign and malignant thyroid dysfunction
Bakhsh, A. (2014) · ORCA Online Research @Cardiff (Cardiff University)
Praxisrelevante Entwicklungen 2011/2012 in der Thyreologie
Feldkamp, J. (2013) · Journal für Kardiologie (Krause & Pachernegg GmbH)
Welcome to the 83rd Annual Meeting of the American Thyroid Association
Koenig, R. J., & Assoc, J. A. S. F. T. A. T. (2013) · Thyroid · doi:10.1089/thy.2013.0486
Functional thyroid gland grown in vitro offers intriguing therapeutic possibility
Mitchell, F. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.197
Disease Modeling and Drug Discovery Using Human Pluripotent Stem Cells
Honoré, C., & Hansson, M. D. (2013) · Stem cell biology and regenerative medicine · doi:10.1007/978-1-4614-8066-2_15
Advances in thyroid development, hormone action and neoplasia
Chatterjee, K. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.253
Congenital Hypothyroidism due to PAX8 Mutations
Narumi, S., & Hasegawa, T. (2015) · Springer eBooks · doi:10.1007/978-3-319-19213-0_7
Cadherin-Based Cell-Cell Adhesions: Adhesion Structure, Signalling and Computational Modeling
Kumar, S., & Sen, S. (2015) · Springer eBooks · doi:10.1007/978-94-017-7380-5_5
Directed Differentiation of Human Pluripotent Stem Cells into Lung and Airway Epithelial Cells
Snoeck, H. (2015) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-319-21082-7_16
Yeo, J. C. (2015) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/62942
A chemical biology study of human embryonic stem cell pluripotency and differentiation
Geng, Y. (2015) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Developmental Approaches to Kidney Regeneration
Benedetti, V., Imberti, B., Xinaris, C., & Remuzzi, G. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801734-0.00075-8
Adewuyi, E. (2016) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3mk65k27
Stem (progenitor) thyroid cells and their probable applications in tissue engeniring
Sergeeva, N. S., Hesuani, Y. D., Poljakov, A. P., Mironov, V. A., & Каприн, А. Д. (2018) · Genes and Cells · doi:10.23868/201808015
Thyroid Transplantation: Past and Future
Rybakov, S. I. (2020) · Clinical endocrinology and endocrine surgery · doi:10.30978/cees-2020-1-96
Thyroid Gland Development, Molecular Biology
Muzza, M., & Fugazzola, L. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.96023-9
Opto-Magneto-Electrical Nanoactuators for Wireless Cell Stimulation
Zhang, Y. (2020) · Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya)
Role of Pcsk9 In The Diagnosis Thyroid Disorder in Patient Women
Mohammed, H. F., & Jaber, S. H. (2021) · Medical Science Journal for Advance Research · doi:10.46966/msjar.v2i1.16
Induced pluripotent stem cell–derived salivary glands
Tanaka, J., & Mishima, K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823809-7.00004-9
Single-cell transcriptome analysis reveals thyrocyte diversity in the zebrafish thyroid gland
Gillotay, P., Shankar, M., Haerlingen, B., Eski, S. E., Pozo‐Morales, M., Suñer, I. G., Reinhardt, S., Kränkel, A., Bläsche, J., Petzold, A., et al. (2021) · Yearbook of pediatric endocrinology · doi:10.1530/ey.18.3.4
Self-citationFelice, M. D., & Lauro, R. D. (2015) · Springer eBooks · doi:10.1007/978-3-319-19213-0_1
Patient Tailored Treatment of Thyroid Cancer: Radiotherapy, Organoid Models and Follow-up
Groen, A. H. (2022) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.231244722
Emerging technologies in thyroid biology: Pushing the frontiers of thyroid research
Costagliola, S., & Singh, S. P. (2023) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2023.111912
Self-citationSaqcena, M., Leandro-Garcia, L. J., Mååg, J. L. V., Tchekmedyian, V., Krishnamoorthy, G. P., Tamarapu, P. P., Tiedje, V., Reuter, V. P., Knauf, J. A., de Stanchina, E., et al. (2023) · doi:10.1158/2159-8290.c.6548987.v1
Self-citationOrganoid-based modality of eye function and cellular processes
El-Hashash, A. H. K. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99987-8.00006-0
Thyroid Stem Cell Speciation—a Major Role for PKC
Latif, R., MORSHED, S. A., McCann, C., & Davies, T. F. (2023) · Endocrinology · doi:10.1210/endocr/bqad067
COMPARATIVE MORPHOLOGY OF THE THYROID GLAND
Sviatotska, L. O. (2023) · Bulletin of Problems Biology and Medicine · doi:10.29254/2077-4214-2023-2-169-386-393 · Cited by 1
Cerebral and noncerebral organoids
Lavazza, A., & Chinaia, A. A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-19045-2.00014-3
Shirai, Y.-T., Hoshi, N., Ward, J. M., Liu, H., Cachau, R. E., Lee, M. P., & Kimura, S. (2023) · Thyroid · doi:10.1089/thy.2023.0341
Organoids in Antiviral Research: Potential and Challenges
Singh, A., Kumar, N., Desai, D. N., Sahu, U., Bhatia, S., Kumar, M., Tripathi, B. N., & Sanyal, A. (2024) · Livestock diseases and management · doi:10.1007/978-981-99-9195-2_4
Acar, Ö. K., Nozhatzadeh, G. D., Kurtoglu, N., & Ayşan, E. (2024) · Springer eBooks · doi:10.1007/978-981-99-7119-0_20
An Introduction to Thyroid Physiology
Bernal, J. (2024) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815274226124010005
Thyroid gland development, molecular biology
Fugazzola, L., & Muzza, M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00180-1
Dupuy, C., Radom, M., Buffet, C., Cazarin, J., Harinquet, M., de Faria, C. C., Brayé, F., Nobre, C., Aglave, M., Mesloub, Y., et al. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5138035
Fifty Years of Support From the NIDDK for a Pioneer in Thyroid Research
Bianco, A. C. (2025) · Endocrinology · doi:10.1210/endocr/bqaf060
NOX4 prevents the recruitment of PAX8 and NKX2.1 to chromatin in BRAF-mutated thyroid cancer cellsPreprint
Radom, M., Buffet, C., Cazarin, J., Harinquet, M., de Faria, C. C., Brayé, F., Nobre, C., Aglave, M., Mesloub, Y., Dayris, T., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.14.647724
Additional file 1 of Organoids: a systematic review of ethical issues
de Jongh, D., Massey, E. K., & Bunnik, E. M. (2022) · Figshare · doi:10.6084/m9.figshare.20364906
Additional file 2 of Organoids: a systematic review of ethical issues
de Jongh, D., Massey, E. K., & Bunnik, E. M. (2022) · Figshare · doi:10.6084/m9.figshare.20364909
Influence of donor–recipient age differences in allogenic rat thyroid transplantation
Arauchi, A., Matsuura, K., & Shimizu, T. (2025) · Regenerative Therapy · doi:10.1016/j.reth.2025.101047
From initiation to maturation: Mesenchymal stem cells as key facilitators in organoid development
Yi, S., Wen, J., Wang, T., Yu, W., Liao, Y., Liu, Z., & Wang, H. (2026) · Cells and Development · doi:10.1016/j.cdev.2026.204071
Radiation-induced interferon-I response impairs thyroid organoid function
Maturi, R., Cinat, D., Bruin, A. L. J.-D., Vita, G. D., Kruijff, S., Coppes, R. P., & Soto-Gamez, A. (2026) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2026.111453
Advances in Thyroid Gland Regeneration: The Integrated Approach of Cell Biology and Bioengineering
Górnicki, T., Soriano, M. G., Raffaele, G., Fortunato, G. M., Jones, W., Cecchettini, A., Szymczyk‐Ziółkowska, P., Kaliszewski, K., Dzięgiel, P., Vozzi, F., et al. (2026) · Tissue Engineering Part B Reviews · doi:10.1177/19373368261431206
Organoid Perturbations as Tools to Explore Cellular Function and Plasticity
Kohl, K. E., & Busslinger, G. A. (2026) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-120324-024252
Unmasking prostate cancer risk factors leveraging organoid technology
Cantarelli, M., Marmocchi, E., Lunardi, A., & Begaj, R. (2026) · Gene · doi:10.1016/j.gene.2026.150142
New molecular insights in pathogenesis of congenital hypothyroidism
Stoupa, A. (2021) · theses.fr (ABES) · doi:10.70675/ba72d900z86edz4200z8ddcz1af6c6d513ae
Mejlachowicz, D. (2020) · theses.fr (ABES) · doi:10.70675/9628ed3ez2da1z4b55zab69z4a24dfdb174b
Engineering next-generation in vitro platforms for endocrine disruptor testing via bioprinting
Sana, M., Mota, C., & Moroni, L. (2026) · Precision medicine and engineering. · doi:10.1016/j.preme.2026.100071
The role of Nrf2 in thyroid maturation and hormone synthesis in vertebrate models
Gillotay, P., Bangru, S., Dassy, B., Haerlingen, B., Shankar, M., Fonseca, B. F., Ziros, P. G., Singh, S. P., Sykiotis, G. P., Romitti, M., et al. (2026) · Life Science Alliance · doi:10.26508/lsa.202603687
Self-citationResolving thyroid lineage cell trajectories merging into a dual endocrine gland in mammals
Lobo, M., Johansson, E., Kumari, S., Schoultz, E., Ahlinder, I., Liang, S., Carlsson, T., Johansson, B. R., Marotta, P., Felice, M. D., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-73385-6
Heim, M., Handley, E., Gao, Y.-X., Mandel, A., Emmerson, E., & Callanan, A. (2026) · Biofabrication · doi:10.1088/1758-5090/ae8bdb
The Application of 3D Cell Culture in Thyroid Cancer
Jiang, H., Zhou, D., Li, Z., Jiang, H., Zhu, G., Xu, K., & Sun, J. (2026) · Annals of Biomedical Engineering · doi:10.1007/s10439-026-04299-z
Tourneur, A., Vitória, J. R., Saiselet, M., Craciun, L., Larsimont, D., Lefort, A., Libert, F., Maenhaut, C., Costagliola, S., Tarabichi, M., et al. (2026) · Molecular Oncology · doi:10.1002/1878-0261.70289 · Cited by 2
Self-citationMa, Y., Jiang, W., Zhou, T., Sun, B., Gong, C.-J., Guan, L., & Wang, Q.-F. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1914528
Dong, L., 彭满珍, Yao, C., Xie, C., & Liu, H. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1885613
Stem cell strategies for cell replacement therapy in endocrine diseases
Mi, C., Xie, C., Tang, J., Gao, Y., Zhang, J., Yang, Y., Tan, G., Zheng, C., & Liu, H. (2026) · Cell Transplantation · doi:10.1177/09636897261486242
Kim, H., Kim, Y. J., Kim, Y. S., So, S., Sung, S., Park, S., Kim, J., Kim, K., Choung, Y.-H., & Ha, J. (2026) · Stem Cells and Development · doi:10.1177/15473287261490309
Embryonic reprogramming drives anaplastic transformation in thyroid carcinoma
Kawaura, R., Unome, A., Tomita, H., Ishihara, H., Kuroki, M., Komura, S., Kato, K., Takashima, S., Nishio, N., Shigeyama, M., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118195
Massively parallel functional genomic assays in endocrinology: from promise to delivery
Xu, J., Aslanzadeh, V., Kudla, G., & Semple, R. K. (2026) · Journal of Molecular Endocrinology · doi:10.1530/jme-25-0134
Metadata
- Authors
- Antonica, F., Kasprzyk, D. F., Opitz, R., Iacovino, M., Liao, X.-H., Dumitrescu, A. M., Refetoff, S., Peremans, K., Manto, M., Kyba, M., & Costagliola, S.
- Affiliations
- Université Libre de Bruxelles (BE)
- University of Minnesota (US)
- University of Chicago (US)
- Ghent University (BE)
- Corresponding author
- Costagliola, Sabine
- ORCID
- Venue
- Nature
- Published
- 2012-10-10
- Volume
- 491
- Issue
- 7422
- Pages
- 66-71
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3687105
- OpenAlex
- W2155574792
- Cited by
- 359
- References
- 78
- Citations by year
- 2026: 18 · 2025: 20 · 2024: 23 · 2023: 26 · 2022: 33 · 2021: 28 · 2020: 33 · 2019: 24 · 2018: 19 · 2017: 18 · 2016: 26 · 2015: 35 · 2014: 27 · 2013: 25 · 2012: 3
- FWCI
- 11.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Iris (University of Trento) (submittedVersion)
- Funders
- Fonds De La Recherche Scientifique - FNRS
- National Institutes of Health (DK 15070)
- Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 15070, R37DK015070, F32DK091016, DK91016, R01DK015070)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- embryonic stem cells, thyroid follicular cells, TTF-1, PAX8, transcription factors, thyroid-stimulating hormone, iodide organification, thyroid hormone synthesis, thyroid development, congenital hypothyroidism, regenerative medicine, stem cell differentiation
- MeSH terms
- PAX8 Transcription Factor, Thyroid Nuclear Factor 1, Animals, Cell Differentiation, Disease Models, Animal, Female, Humans, Hypothyroidism, Nuclear Proteins, Thyroid Gland, Thyrotropin, Thyroxine, Transcription Factors, Mice, Paired Box Transcription Factors, Embryonic Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
