Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.
Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.
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DOI：
10.1371/journal.pone.0027360
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Pirvola U
中科院分区：
文献类型：
--
作者：
Loponen H;Ylikoski J;Albrecht JH;Pirvola U
哺乳动物内耳的感觉毛细胞和支持细胞是静止细胞，不会再生。相比之下，非哺乳动物支持细胞具有重新进入细胞周期并产生替代毛细胞的能力。早期研究表明，细胞周期蛋白 D1 在发育中的小鼠支持细胞中表达，并且随着成熟过程的下调。在小鼠椭圆囊的外植体培养中，我们重点研究成体支持细胞的细胞周期控制机制和增殖潜力。这些细胞通过腺病毒介导的细胞周期蛋白 D1 过度表达被迫进入细胞周期。异位细胞周期蛋白 D1 触发支持细胞的强劲细胞周期重新进入，并伴随着 p27Kip1 和 p21Cip1 表达的变化。细胞周期重新激活的支持细胞的主要部分被DNA损伤并停滞在G2/M边界。仅发现少量有丝分裂支持细胞和具有两次连续复制迹象的稀有细胞。异位细胞周期蛋白 D1 触发的细胞周期重新激活不会导致感觉上皮增生。此外，异位细胞周期蛋白D1的一部分被隔离在细胞质中，反映出其无效的核输入。综合起来，我们的数据揭示了限制椭圆囊支持细胞增殖能力的内在障碍。
Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27Kip1 and p21Cip1 expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.
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影响因子：
2.7
作者：
Laine, Heidi;Sulg, Marilin;Pirvola, Ula
通讯作者：
Pirvola, Ula
影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
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64.5
作者：
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Kuehn, Bernhard
影响因子：
56.9
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Vogelstein, B
影响因子：
4.3
作者：
Huang, Mingqian;Sage, Cyrille;Chen, Zheng-Yi
通讯作者：
Chen, Zheng-Yi