Department of Biological Science, Graduate School of Science, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Biochem Biophys Res Commun. 2010 Oct 8;401(1):1-6. doi: 10.1016/j.bbrc.2010.08.099. Epub 2010 Aug 31.
Motile cilia play crucial roles in the maintenance of homeostasis in vivo. Defects in the biosynthesis of cilia cause immotile cilia syndrome, also known as primary ciliary dyskinesia (PCD), which is associated with a variety of complex diseases. In this study, we found that inhibitory Smad proteins, Smad7 and Smad6, significantly promoted the differentiation of mouse embryonic stem (ES) cells into ciliated cells. Moreover, these Smad proteins specifically induced morphologically distinct Musashi1-positive ciliated cells. These results suggest that inhibitory Smad proteins could be important regulators not only for the regulation of ciliated cell differentiation, but also for the subtype specification of ciliated cells during differentiation from mouse ES cells.
纤毛在体内维持内稳态方面发挥着关键作用。纤毛生物合成缺陷导致不动纤毛综合征,也称为原发性纤毛运动障碍(PCD),与多种复杂疾病相关。在这项研究中,我们发现抑制性 Smad 蛋白 Smad7 和 Smad6 显著促进了小鼠胚胎干细胞(ES 细胞)向纤毛细胞的分化。此外,这些 Smad 蛋白特异性地诱导了形态上不同的 Musashi1 阳性纤毛细胞。这些结果表明,抑制性 Smad 蛋白不仅可以作为纤毛细胞分化的重要调节因子,而且可以作为从小鼠 ES 细胞分化过程中纤毛细胞亚型特化的重要调节因子。