Morphogenetics of early thyroid development

Fagman, Henrik; Nilsson, Mikael

doi:10.1677/jme-10-0084

Cited by 87 publications

(84 citation statements)

References 96 publications

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“…Human thyroid development is regulated at the transcriptional level involving primarily four different factors-PAX8, NKX2-1, HEX, and FOXE1-and controlled by various morphogens, particularly NODAL factors regulating the endoderm formation at gastrulation (5,6). Thyroid cells are derived from endoderm that develops from pluripotent cells in the early embryo.…”

mentioning

confidence: 99%

Human Embryonic Stem Cells Form Functional Thyroid Follicles

Latif

Davies

2015

Thyroid

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Objective: The 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. Methods: Reporter 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). Results: Both 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 dosedependent cAMP generation and radioiodine uptake, indicating functional thyroid epithelial cells. Conclusion: The 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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mentioning

confidence: 99%

Human Embryonic Stem Cells Form Functional Thyroid Follicles

Latif

Davies

2015

Thyroid

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“…Among all the genetic factors, FOXE1 plays an important role in the morphogenetic process which is regulated by both cell-autonomous and mesoderm-derived mechanisms acting in concert to promote growth and survival of progenitor cells [19,20]. In other studies, the FOXE1 variants were associated with the risk of DTC in some populations, including Spain, Belarusian, Portuguese, et al [7,11,21,22].…”

Section: Discussionmentioning

confidence: 94%

Association between FOXP3, FOXE1 Gene Polymorphisms and Risk of Differentiated Thyroid Cancer in Chinese Han Population

Zheng¹,

Zhang²

2015

Mol Biol

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“…For example, the foregut identity is closely linked to the expression of HHEX, FOXA2, and SOX2 genes [19]. Thyroid gland precursors arise at the level of the mid-hindbrain boundary closely opposed to the anterior lateral plate of mesoderm from which the heart develops [20]. The thyroid anlage is the first part to develop during organogenesis of thyroid gland.…”

Section: Discussionmentioning

confidence: 99%