...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Single cell heterogeneity: Why unstable genomes are incompatible with average profiles
【24h】

Single cell heterogeneity: Why unstable genomes are incompatible with average profiles

机译：单细胞异质性：为什么不稳定的基因组与平均谱不兼容

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Multi-level heterogeneity is a fundamental but underappreciated feature of cancer. Most technical and analytical methods either completely ignore heterogeneity or do not fully account for it, as heterogeneity has been considered noise that needs to be eliminated. We have used single-cell and population-based assays to describe an instability-mediated mechanism where genome heterogeneity drastically affects cell growth and cannot be accurately measured using conventional averages. First, we show that most unstable cancer cell populations exhibit high levels of karyotype heterogeneity, where it is difficult, if not impossible, to karyotypically clone cells. Second, by comparing stable and unstable cell populations, we show that instability-mediated karyotype heterogeneity leads to growth heterogeneity, where outliers dominantly contribute to population growth and exhibit shorter cell cycles. Predictability of population growth is more difficult for heterogeneous cell populations than for homogenous cell populations. Since "outliers" play an important role in cancer evolution, where genome instability is the key feature, averaging methods used to characterize cell populations are misleading. Variances quantify heterogeneity; means (averages) smooth heterogeneity, invariably hiding it. Cell populations of pathological conditions with high genome instability, like cancer, behave differently than karyotypically homogeneous cell populations. Single-cell analysis is thus needed when cells are not genomically identical. Despite increased attention given to single-cell variation mediated heterogeneity of cancer cells, continued use of averagebased methods is not only inaccurate but deceptive, as the "average" cancer cell clearly does not exist. Genome-level heterogeneity also may explain population heterogeneity, drug resistance, and cancer evolution.
机译：多级异质性是癌症的基本但未被重视的特征。大多数技术和分析方法要么完全忽略异质性，要么不完全考虑异质性，因为异质性被认为是需要消除的噪声。我们已经使用基于单细胞和群体的分析方法来描述不稳定性介导的机制，其中基因组异质性极大地影响细胞生长，无法使用常规平均值准确测量。首先，我们表明大多数不稳定的癌细胞群都表现出高水平的核型异质性，如果不是不可能的话，很难以核型克隆细胞。第二，通过比较稳定和不稳定的细胞群体，我们表明，不稳定性介导的核型异质性导致生长异质性，其中离群值显着地促进了群体生长并表现出较短的细胞周期。对于异质细胞群体，种群增长的可预测性要比同质细胞群体困难。由于“异常值”在癌症进化中起着重要作用，而基因组不稳定性是关键特征，因此用于表征细胞群的平均方法具有误导性。方差量化异质性;表示（平均）平滑的异质性，总是将其隐藏。具有高基因组不稳定性的病理状况的细胞群（例如癌症）的行为不同于核型同质的细胞群。因此，当细胞在基因组上不相同时，需要进行单细胞分析。尽管越来越多地关注单细胞变异介导的癌细胞异质性，但继续使用基于平均值的方法不仅不准确而且具有欺骗性，因为“平均”癌细胞显然不存在。基因组水平的异质性也可以解释群体异质性，耐药性和癌症演变。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号