Uncoordinated centrosome cycle underlies the instability of non-diploid somatic cells in mammals.
Uncoordinated centrosome cycle underlies the instability of non-diploid somatic cells in mammals.
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DOI：
10.1083/jcb.201701151
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发表时间：
2018-07-02
期刊：
影响因子：
--
通讯作者：
Uehara R
中科院分区：
文献类型：
--
作者：
Yaguchi K;Yamamoto T;Matsui R;Tsukada Y;Shibanuma A;Kamimura K;Koda T;Uehara R
哺乳动物体细胞作为二倍体更稳定，但这种稳定性背后的机制尚不清楚。Yaguchi等人。结果表明，中心粒许可的变化损害了单倍体或四倍体人类细胞中心体数的控制，这表明中心体周期的倍性依赖控制解释了非二倍体核型的不稳定性。在动物中，体细胞通常是二倍体，单倍体时不稳定，原因不明。在这项研究中，通过比较不同倍体的同基因人类细胞系，我们发现在单倍体状态下频繁的中心体丢失，这在随后的有丝分裂缺陷中深刻地导致了单倍体的不稳定性。我们还发现，中心粒许可和复制的效率与倍性水平成比例变化，而DNA复制的效率保持不变。这分别导致单倍体和四倍体细胞中中心粒的逐渐丢失或频繁重复。中心粒的许可效率似乎受星形微管的调节，星形微管的发育与倍性水平有关，人工促进单倍体细胞中星形核的形成使中心粒的许可效率恢复到二倍体水平。在不同类型的哺乳动物细胞中观察到了倍性-中心体联系。我们认为，中心体复制和DNA复制周期之间的不相容是哺乳动物非二倍体体细胞不稳定的基础，这些不同的生物过程在倍性变化时具有不同的缩放特性。
Mammalian somatic cells are more stable as diploids, but the mechanisms underlying this stability are unclear. Yaguchi et al. show that changes in centriole licensing compromise the control of centrosome number in haploid or tetraploid human cells, suggesting that the ploidy-dependent control of the centrosome cycle explains the instability of non-diploid karyotypes. In animals, somatic cells are usually diploid and are unstable when haploid for unknown reasons. In this study, by comparing isogenic human cell lines with different ploidies, we found frequent centrosome loss specifically in the haploid state, which profoundly contributed to haploid instability through subsequent mitotic defects. We also found that the efficiency of centriole licensing and duplication changes proportionally to ploidy level, whereas that of DNA replication stays constant. This caused gradual loss or frequent overduplication of centrioles in haploid and tetraploid cells, respectively. Centriole licensing efficiency seemed to be modulated by astral microtubules, whose development scaled with ploidy level, and artificial enhancement of aster formation in haploid cells restored centriole licensing efficiency to diploid levels. The ploidy–centrosome link was observed in different mammalian cell types. We propose that incompatibility between the centrosome duplication and DNA replication cycles arising from different scaling properties of these bioprocesses upon ploidy changes underlies the instability of non-diploid somatic cells in mammals.
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DOI：
10.1083/jcb.201202135
发表时间：
2012-08-06
期刊：
The Journal of cell biology
影响因子：
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DOI：
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发表时间：
2010-11-15
期刊：
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影响因子：
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作者：
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