Abstract：
The parathyroid gland plays an essential role in mineral and bone metabolism. Cultivation of physiological human parathyroid cells has yet to be established and the method by which parathyroid cells differentiate from pluripotent stem cells remains uncertain. Therefore, it has been hard to clarify the mechanisms underlying the onset of parathyroid disorders, such as hyperparathyroidism. In this study, we developed a new method of parathyroid cell differentiation from human induced pluripotent stem (iPS) cells. Parathyroid cell differentiation occurred in accordance with embryologic development. Differentiated cells, which expressed the parathyroid hormone, adopted unique cell aggregation similar to the parathyroid gland. In addition, these differentiated cells were identified as calcium-sensing receptor (CaSR)/epithelial cell adhesion molecule (EpCAM) double-positive cells. Interestingly, stimulation with transforming growth factor-α (TGF-α), which is considered a causative molecule of parathyroid hyperplasia, increased the CaSR/EpCAM double-positive cells, but this effect was suppressed by erlotinib, which is an epidermal growth factor receptor (EGFR) inhibitor. These results suggest that TGF-α/EGFR signaling promotes parathyroid cell differentiation from iPS cells in a similar manner to parathyroid hyperplasia.
摘要：
甲状旁腺在矿物质和骨代谢中起着至关重要的作用。生理性人甲状旁腺细胞的培养尚未建立，甲状旁腺细胞从多能干细胞分化的方法仍不确定。因此,很难澄清甲状旁腺疾病发病的潜在机制，如甲状旁腺功能亢进。在这项研究中,我们开发了一种从人类诱导多能干细胞（iPS）分化甲状旁腺细胞的新方法。甲状旁腺细胞分化与胚胎发育一致。分化细胞,表达甲状旁腺激素，采用类似于甲状旁腺的独特细胞聚集。此外,这些分化的细胞被鉴定为钙敏感受体（CaSR）/上皮细胞粘附分子（EpCAM）双阳性细胞。有趣的是,用转化生长因子-α（TGF-α）刺激，它被认为是甲状旁腺增生的致病分子，增加了CaSR/EpCAM双阳性细胞，但是这种作用被厄洛替尼抑制了，它是一种表皮生长因子受体（EGFR）抑制剂。这些结果表明TGF-α/EGFR信号传导以类似于甲状旁腺增生的方式促进甲状旁腺细胞从iPS细胞分化。
