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The essentiality landscape of cell cycle related genes in human pluripotent and cancer cells

机译：细胞周期相关基因在人多能和癌细胞中的基础景观

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Cell cycle regulation is a complex system consisting of growth-promoting and growth-restricting mechanisms, whose coordinated activity is vital for proper division and propagation. Alterations in this regulation may lead to uncontrolled proliferation and genomic instability, triggering carcinogenesis. Here, we conducted a comprehensive bioinformatic analysis of cell cycle-related genes using data from CRISPR/Cas9 loss-of-function screens performed in four cancer cell lines and in human embryonic stem cells (hESCs). Cell cycle genes, and in particular S phase and checkpoint genes, are highly essential for the growth of cancer and pluripotent cells. However, checkpoint genes are also found to underlie the differences between the cell cycle features of these cell types. Interestingly, while growth-promoting cell cycle genes overlap considerably between cancer and stem cells, growth-restricting cell cycle genes are completely distinct. Moreover, growth-restricting genes are consistently less frequent in cancer cells than in hESCs. Here we show that most of these genes are regulated by the tumor suppressor gene TP53, which is mutated in most cancer cells. Therefore, the growth-restriction system in cancer cells lacks important factors and does not function properly. Intriguingly, M phase genes are specifically essential for the growth of hESCs and are highly abundant among hESC-enriched genes. Our results highlight the differences in cell cycle regulation between cell types and emphasize the importance of conducting cell cycle studies in cells with intact genomes, in order to obtain an authentic representation of the genetic features of the cell cycle.
机译：细胞周期调节是一种复杂的系统，包括增长促进和生长限制机制，其协调活性对于适当的分裂和繁殖至关重要。该调节的改变可能导致不受控制的增殖和基因组不稳定性，引发致癌作用。在这里，我们使用来自四种癌细胞系和人胚胎干细胞（HESC）中的CRISPR / CAS9失去功能屏幕的数据进行了对细胞周期相关基因的综合生物信息分析。细胞周期基因，特别是S期和检查点基因对癌症和多能细胞的生长来说是非常重要的。然而，还发现检查点基因利于这些细胞类型的细胞周期特征之间的差异。有趣的是，虽然生长促进细胞周期基因在癌症和干细胞之间重叠，但增长限制细胞周期基因是完全不同的。此外，生长限制基因在癌细胞中持续低于HESC。在这里，我们表明大多数这些基因由肿瘤抑制基因TP53调节，其在大多数癌细胞中突变。因此，癌细胞中生长限制系统缺乏重要因素，并且无法正常运作。有趣的是，M相基因对于HESC的生长特别是必不可少的，并且在富集的基因中具有高度丰富。我们的结果突出了细胞类型之间细胞周期调节的差异，并强调了在具有完整基因组的细胞中进行细胞周期研究的重要性，以获得细胞周期的遗传特征的真实表示。

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