ArticleThyroid : official journal of the American Thyroid Association2015
Human embryonic stem cells form functional thyroid follicles.
Article in Thyroid : official journal of the American Thyroid Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Engineering a functional thyroid as a potential therapeutic substitute for hypothyroidism treatment: A systematic review.Frontiers in endocrinology · 2022Pooled it
- Human thyroid organoids: tools for understanding thyroid diseases and development.Nature reviews. Endocrinology · 2026Review
- Endocrinology at a Miniature Level: Pluripotent Stem-Cell-Derived Organoid Models of Hypothalamus-Pituitary Axes.Biomolecules · 2026Review
- Influence of donor-recipient age differences in allogenic rat thyroid transplantation.Regenerative therapy · 2026Article
- Article
- Functional Thyroid Organoids-Powerful Stem Cell-Derived Models in Basic and Translational Research.Biomolecules · 2025Review
- Article
- Article
- Regeneration of Thyroid Glands in the Spleen Restores Homeostasis in Thyroidectomy Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids.Oncogene · 2024Article
- Advances in the Construction and Application of Thyroid Organoids.Physiological research · 2023Review
- Thyroid hormone receptor α1: a novel regulator of thyroid cancer cell differentiation.Oncogene · 2023Article
- Progress Toward and Challenges Remaining for Thyroid Tissue Regeneration.Endocrinology · 2023Review
- Thyroid-on-a-Chip: An Organoid Platform for In Vitro Assessment of Endocrine Disruption.Advanced healthcare materials · 2023Article
- Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism.Nature communications · 2022Article
- Stem Cell Therapy for Thyroid Diseases: Progress and Challenges.Current therapeutic research, clinical and experimental · 2022Review
- From hormone replacement therapy to regenerative scaffolds: A review of current and novel primary hypothyroidism therapeutics.Frontiers in endocrinology · 2022Review
- Organoids as Model Systems to Investigate Circadian Clock-Related Diseases and Treatments.Frontiers in genetics · 2022Review
- The Transient Human Thyroid Progenitor Cell: Examining the Thyroid Continuum from Stem Cell to Follicular Cell.Thyroid : official journal of the American Thyroid Association · 2021Review
- Derivation of Thyroid Follicular Cells From Pluripotent Stem Cells: Insights From Development and Implications for Regenerative Medicine.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe molecular events that lead to human thyroid cell speciation remain incompletely characterized. It has been shown that overexpression of the regulatory transcription factors Pax8 and Nkx2-1 (ttf-1) directs murine embryonic stem (mES) cells to differentiate into thyroid follicular cells by initiating a transcriptional regulatory network. Such cells subsequently organized into three-dimensional follicular structures in the presence of extracellular matrix. In the current study, human embryonic stem (hES) cells were studied with the aim of recapitulating this scenario and producing functional human thyroid cell lines.
methodsReporter gene tagged pEZ-lentiviral vectors were used to express human PAX8-eGFP and NKX2-1-mCherry in the H9 hES cell line followed by differentiation into thyroid cells directed by Activin A and thyrotropin (TSH).
resultsBoth transcription factors were expressed efficiently in hES cells expressing either PAX8, NKX2-1, or in combination in the hES cells, which had low endogenous expression of these transcription factors. Further differentiation of the double transfected cells showed the expression of thyroid-specific genes, including thyroglobulin (TG), thyroid peroxidase (TPO), the sodium/iodide symporter (NIS), and the TSH receptor (TSHR) as assessed by reverse transcription polymerase chain reaction and immunostaining. Most notably, the Activin/TSH-induced differentiation approach resulted in thyroid follicle formation and abundant TG protein expression within the follicular lumens. On stimulation with TSH, these hES-derived follicles were also capable of dose-dependent cAMP generation and radioiodine uptake, indicating functional thyroid epithelial cells.
conclusionThe induced expression of PAX8 and NKX2-1 in hES cells was followed by differentiation into thyroid epithelial cells and their commitment to form functional three-dimensional neo-follicular structures. The data provide proof of principal that hES cells can be committed to thyroid cell speciation under appropriate conditions.
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