Project description:The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of adult stem cell-derived three-dimensional (3D) organoids representing murine and human thyroid follicular cells (TFCs). The TFC organoids (TFCO) harbour the complete machinery of hormone production as visualised by the presence of colloid in the lumen and by the presence of essential transporters and enzymes in the polarised 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.
Project description:The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of adult stem cell-derived three-dimensional (3D) organoids representing murine and human thyroid follicular cells (TFCs). The TFC organoids (TFCO) harbour the complete machinery of hormone production as visualised by the presence of colloid in the lumen and by the presence of essential transporters and enzymes in the polarised 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.
Project description:The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of adult stem cell-derived three-dimensional (3D) organoids representing murine and human thyroid follicular cells (TFCs). The TFC organoids (TFCO) harbour the complete machinery of hormone production as visualised by the presence of colloid in the lumen and by the presence of essential transporters and enzymes in the polarised 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.
Project description:Follicular thyroid tumours were investigated using global gene expression analysis. Aim of this study was the identification of new markers for follicular thyroid carcinoma. Keywords: cell type comparison Gene expression analysis of 4 follicular thyroid adenomas, 4 follicular thyroid carcinomas, and 4 microinvasive follicular thyroid carcinomas.
Project description:Follicular thyroid tumours were investigated using global gene expression analysis. Aim of this study was the identification of new markers for follicular thyroid carcinoma. Keywords: cell type comparison
Project description:Defined transcription factors can direct changes in programmed cell fate to give rise to various cell lineages, in contrast to the one-way street during development. Direct lineage conversions from fibroblasts occur in all the three germ layer derivatives- neurons, cardiomyocytes, and hepatocytes. However, direct reprogramming of thyroid lineages has not been accomplished yet. Previous studies demonstrated that exogenous Pax8 and Nkx2.1, which are indispensable for proper thyroid development, enable the pluripotent stem cell-derived definitive endoderm to differentiate into functional thyroid follicular cells. This raised the question whether a cocktail of thyroid development-related transcription factors can directly convert fibroblasts into thyroid follicular cells in vitro. In the current study, we found that induction of defined transcription factors is able to generate thyroid follicular cells from fibroblasts. Further, Pax8, Nkx2.1, Foxe1, Oct3/4, Sox2, Klf4, and c-Myc were sufficient to generate thyroglobulin (Tg)+/EpCAM+ colonies from mouse embryonic fibroblasts, and these colonies built three-dimensional (3D) follicular-like structures in matrigel-based 3D culture. These induced thyroid follicular-like cells, named iTF cells, were morphologically and transcriptionally similar to those of the adult thyroid. Finally, iTF cells were transplantable into the kidney capsule, and formed huge follicular structures in vivo as well. Our study therefore reveals that thyroid lineage can be directly derived from fibroblasts in a single step, and contributes to rapid translational research on human thyroid diseases such as hyperthyroidism.