Transcriptional profiles of induced thyroid follicular like cells.. Mus musculus

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. Overall design: We generated arrays from Pax8, Nkx2.1, Foxe1, Hhex, Oct3/4, Sox2, Klf4, and c-Myc induced thyroid follicular-like cells derived from fibroblast cutures. In addition, we also generated arrays from primary thyroid follicular cell cultures as controls. All the datas were normalized to 75% tile shift..