Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Thyroid and Endocrinology, Fukushima Medical University, Fukushima, 960-1295, Japan.
Lab Invest. 2018 Sep;98(9):1126-1132. doi: 10.1038/s41374-018-0068-x. Epub 2018 Jun 26.
While thyroid is considered to be a dormant organ, when required, it can regenerate through increased cell proliferation. However, the mechanism for regeneration remains unknown. Nkx2-1(fl/fl);TPO-cre mouse thyroids exhibit a very disorganized appearance because their thyroids continuously degenerate and regenerate. In mouse thyroids, a cluster of cells are found near the tracheal cartilage and muscle, which are positive for expression of NKX2-1, the master transcription factor governing thyroid development and function. In the present study, we propose that this cluster of NKX2-1-positive cells may be the precursor cells that mature to become thyroid follicular cells, forming thyroid follicles. We also found that phosphorylation of AKT is induced by NKX2-1 in the proposed thyroid progenitor-like side-population cell-derived thyroid cell line (SPTL) cells, suggesting the possibility that NKX2-1 plays a role in differentiation through the modulation of AKT signaling. This study revealed that Nkx2-1(fl/fl);TPO-cre mice provide a suitable model to study in vivo regeneration and folliculogenesis of the thyroid.
虽然甲状腺被认为是一个休眠的器官,但在需要时,它可以通过细胞增殖增加来再生。然而,再生的机制仍然未知。Nkx2-1(fl/fl);TPO-cre 小鼠的甲状腺表现出非常紊乱的外观,因为它们的甲状腺不断退化和再生。在小鼠的甲状腺中,在气管软骨和肌肉附近发现了一群细胞,这些细胞对 NKX2-1 的表达呈阳性,NKX2-1 是控制甲状腺发育和功能的主转录因子。在本研究中,我们提出,这群 NKX2-1 阳性细胞可能是前体细胞,它们成熟为甲状腺滤泡细胞,形成甲状腺滤泡。我们还发现,在拟议的甲状腺祖细胞样侧群细胞衍生的甲状腺细胞系 (SPTL) 细胞中,AKT 的磷酸化是由 NKX2-1 诱导的,这表明 NKX2-1 通过调节 AKT 信号转导在分化中发挥作用的可能性。这项研究表明,Nkx2-1(fl/fl);TPO-cre 小鼠为研究甲状腺的体内再生和滤泡发生提供了一个合适的模型。