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.

中文翻译：

---

人类多能细胞和癌细胞中细胞周期相关基因的本质景观

细胞周期调控是一个由促进生长和抑制生长的机制组成的复杂系统，其协同活动对于正常的分裂和增殖至关重要。这种调节的改变可能导致不受控制的增殖和基因组不稳定，从而引发致癌作用。在这里，我们使用来自在四种癌细胞系和人类胚胎干细胞 (hESCs) 中进行的 CRISPR/Cas9 功能丧失筛选的数据，对细胞周期相关基因进行了全面的生物信息学分析。细胞周期基因，特别是 S 期和检查点基因，对癌细胞和多能细胞的生长非常重要。然而，检查点基因也被发现是这些细胞类型的细胞周期特征之间差异的基础。有趣的是，虽然促进生长的细胞周期基因在癌症和干细胞之间有很大重叠，但限制生长的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的频率始终低于在 hESC 中的频率。在这里，我们显示这些基因中的大多数受抑癌基因 TP53 的调节，该基因在大多数癌细胞中发生突变。因此，癌细胞中的生长限制系统缺乏重要因素，无法正常发挥作用。有趣的是，M 期基因对于 hESC 的生长特别重要，并且在富含 hESC 的基因中非常丰富。我们的研究结果突出了细胞类型之间细胞周期调控的差异，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，