BACKGROUND Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. Quiescent cells also extend a primary cilium, which functions as a signaling hub. Primary cilia have been shown to be important in multiple developmental processes, and are implicated in numerous developmental disorders. Although the association of the cilium with G0 is established, the role of the cilium in the control of the quiescence program is still poorly understood. RESULTS Primary cilia are dynamically regulated across different states of cell cycle exit in skeletal muscle myoblasts: quiescent myoblasts elaborate a primary cilium in vivo and in vitro, but terminally differentiated myofibers do not. Myoblasts where ciliogenesis is ablated using RNAi against a key ciliary assembly protein (IFT88) can exit the cell cycle but display an altered quiescence program and impaired self-renewal. Specifically, the G0 transcriptome in IFT88 knockdown cells is aberrantly enriched for G2/M regulators, suggesting a focused repression of this network by the cilium. Cilium-ablated cells also exhibit features of activation including enhanced activity of Wnt and mitogen signaling and elevated protein synthesis via inactivation of the translational repressor 4E-BP1. CONCLUSIONS Taken together, our results show that the primary cilium integrates and dampens proliferative signaling, represses translation and G2/M genes, and is integral to the establishment of the quiescence program.

中文翻译：

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初级纤毛抑制增殖信号并抑制静止成肌细胞中的 G2/M 转录网络。

背景可逆性细胞周期停滞（静止/G0）是成体干细胞的特征，并且在多个水平上受到主动控制。静止细胞还会延伸初级纤毛，充当信号中枢。初级纤毛已被证明在多种发育过程中很重要，并且与许多发育障碍有关。尽管纤毛与 G0 的关联已被确立，但纤毛在控制静止程序中的作用仍然知之甚少。结果初级纤毛在骨骼肌成肌细胞的细胞周期退出的不同状态下受到动态调节：静止的成肌细胞在体内和体外形成初级纤毛，但终末分化的肌纤维则不然。使用针对关键纤毛组装蛋白 (IFT88) 的 RNAi 消除纤毛生成的成肌细胞可以退出细胞周期，但表现出改变的静止程序和受损的自我更新。具体来说，IFT88 敲低细胞中的 G0 转录组异常富集 G2/M 调节因子，表明纤毛对该网络的集中抑制。纤毛消除的细胞还表现出激活特征，包括 Wnt 和有丝分裂原信号传导活性增强，以及通过翻译阻遏物 4E-BP1 失活提高蛋白质合成。结论 综上所述，我们的结果表明初级纤毛整合并抑制增殖信号，抑制翻译和 G2/M 基因，并且是静止程序建立的组成部分。