Department of Respiratory Medicine, National Clinical Research Center of Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
Biochem Biophys Res Commun. 2024 Nov 26;735:150428. doi: 10.1016/j.bbrc.2024.150428. Epub 2024 Jul 20.
Primary ciliary dyskinesia (PCD) is a group of genetically heterogeneous disorders characterized by clinical manifestations resulting from abnormal ciliary motility. Mutations in critical genes, such as Cyclin O (CCNO), have been associated with severe respiratory disease, though limited data are currently available. Here we show that CCNO deficient ciliated cells can only form a reduced number of fully functional centrioles that can mature into ciliated basal bodies, and their transport and anchoring to the top of the plasma membrane are abnormal. Furthermore, we observed that CCNO localizes not only in the cytoplasm but also in the nucleus during the early stages of ciliogenesis, and this dual localization persists into adulthood. Transcriptome analysis revealed downregulation of genes involved in cilia assembly and movement, along with altered transcription factors associated with ciliation upon CCNO depletion. These findings indicate that CCNO may serve as a key regulator in the transcriptional regulation of multiciliogenesis.
原发性纤毛运动障碍（PCD）是一组遗传异质性疾病，其临床表现源于纤毛运动异常。关键基因（如 Cyclin O [CCNO]）的突变与严重的呼吸道疾病有关，但目前可用的数据有限。在这里，我们表明，CCNO 缺陷的纤毛细胞只能形成数量减少的完全功能性中心粒，这些中心粒可以成熟为有纤毛的基底体，其运输和锚定到质膜顶部是异常的。此外，我们观察到 CCNO 在纤毛发生的早期不仅定位在细胞质中，而且还定位在核中，这种双重定位一直持续到成年期。转录组分析显示，CCNO 缺失后，与纤毛组装和运动相关的基因表达下调，同时与纤毛发生相关的转录因子也发生改变。这些发现表明，CCNO 可能作为多纤毛发生的转录调控中的关键调节因子。
