Chromosome-specific nonrandom sister chromatid segregation during stem-cell division.

Chromosome-specific nonrandom sister chromatid segregation during stem-cell division.
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DOI:
10.1038/nature12106
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发表时间:
2013-06-13
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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成体干细胞经历不对称的细胞分裂以自我更新并产生分化细胞,形成成熟组织。姐妹染色单体可能在不对称分裂的干细胞中被区分和非随机分离,尽管其潜在的机制和目的可能仍然是难以捉摸的。我们建立了单染色体分辨率的CO-FISH(染色体取向荧光原位杂交)技术,发现在果蝇雄性生殖系干细胞(GSCs)的不对称分裂过程中,X和Y染色体的姐妹染色单体非随机分离,而不是常染色体。这提供了第一个直接证据,两个姐妹染色单体含有相同的遗传信息可以区分和分离非随机在非对称干细胞分裂。我们进一步证明中心体、SUN-KASH核包膜蛋白和Dnmt2是非随机姐妹染色单体分离所必需的。我们的数据表明,在双亲配子发生过程中,X染色体和Y染色体上能够实现非随机分离的信息被启动。此外,我们发现姐妹染色单体分离在过增殖和去分化的GSC中是随机的。我们提出非随机姐妹染色单体分离可能有助于将携带在两个姐妹染色单体上的不同信息传递给不对称分裂干细胞的子细胞。
Adult stem cells undergo asymmetric cell division to self-renew and give rise to differentiated cells that comprise mature tissue. Sister chromatids may be distinguished and segregated non-randomly in asymmetrically dividing stem cells, although the underlying mechanism and the purpose it may serve remain elusive. We developed the CO-FISH (chromosome orientation fluorescence in situ hybridization) technique with single-chromosome resolution and show that sister chromatids of X and Y chromosomes, but not autosomes, are segregated non-randomly during asymmetric divisions of Drosophila male germline stem cells (GSCs). This provides the first direct evidence that two sister chromatids containing identical genetic information can be distinguished and segregated non-randomly during asymmetric stem cell divisions. We further show that the centrosome, SUN-KASH nuclear envelope proteins, and Dnmt2 are required for non-random sister chromatid segregation. Our data suggest that the information on X and Y chromosomes that enables non-random segregation is primed during gametogenesis in the parents. Moreover, we show that sister chromatid segregation is randomized in GSC overproliferation and dedifferentiated GSCs. We propose that non-random sister chromatid segregation may serve to transmit distinct information carried on two sister chromatids to the daughters of asymmetrically dividing stem cells.
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