Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells.
Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells.
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DOI：
10.1038/msb.2012.40
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发表时间：
2012
影响因子：
9.9
通讯作者：
中科院分区：
文献类型：
--
作者：
额外的染色体拷贝会显著改变真核细胞的生理机能，但其根本原因尚不清楚。我们建立了人类三体和四体细胞系，并确定了与二倍体细胞相比，其转录组和蛋白质组的定量变化。我们发现，虽然转录水平反映了染色体拷贝数的变化，但一些蛋白质的丰度，如蛋白质复合物和蛋白质激酶的亚基，向二倍体水平降低。此外，利用定量数据，我们研究了响应于非整倍体的细胞通路的变化。该分析揭示了具有额外染色体的细胞中通路调节的特异性和一致性改变。例如，DNA和RNA代谢途径下调，而能量代谢、膜代谢和溶酶体途径等几种途径上调。特别是，我们发现p62依赖的选择性自噬在人类三体和四体细胞中被激活。我们的数据提出了第一个广泛的蛋白质组学分析人类细胞异常核型，并提出了一个统一的细胞反应的存在下，额外的染色体。
Extra chromosome copies markedly alter the physiology of eukaryotic cells, but the underlying reasons are not well understood. We created human trisomic and tetrasomic cell lines and determined the quantitative changes in their transcriptome and proteome in comparison with their diploid counterparts. We found that whereas transcription levels reflect the chromosome copy number changes, the abundance of some proteins, such as subunits of protein complexes and protein kinases, is reduced toward diploid levels. Furthermore, using the quantitative data we investigated the changes of cellular pathways in response to aneuploidy. This analysis revealed specific and uniform alterations in pathway regulation in cells with extra chromosomes. For example, the DNA and RNA metabolism pathways were downregulated, whereas several pathways such as energy metabolism, membrane metabolism and lysosomal pathways were upregulated. In particular, we found that the p62-dependent selective autophagy is activated in the human trisomic and tetrasomic cells. Our data present the first broad proteomic analysis of human cells with abnormal karyotypes and suggest a uniform cellular response to the presence of an extra chromosome.
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