在11种瘤类型的癌症转变过程中表观遗传调节
Nadezhda V Terekhanova1,2, Alla Karpova1,2, Wen-Wei Liang1,2
1Department of Medicine, Washington University in St Louis, St Louis, MO, USA.
Nature
|November 2, 2023
概括
这项研究通过分析超过一百万个细胞, 揭示了癌症发病和转移的关键表观遗传驱动因素. 这些发现突显了表观遗传变化,基因表达和癌症进展中的遗传因素之间的相互作用.
科学领域:
- 基因组学
- 表观遗传学
- 癌症生物学
背景情况:
- 染色体可访问性调节基因表达和细胞身份, 这对于了解癌症至关重要.
- 染色质可访问性的变化与癌症的发病,进展和转移有关.
- 与遗传因素相比,瘤转变的表观遗传驱动因素的理解较少.
研究的目的:
- 构建一个全癌症表观遗传和转录基因图谱.
- 使用单核染色体可访问性和RNA测序数据识别与癌症转变相关的表观遗传驱动因素.
- 研究增强剂可访问性和基因表达之间的相关性,并揭示表观遗传和遗传驱动因素之间的合作.
主要方法:
- 在225个癌症样本上使用单核测定可转移酶可访问的染色体 (snATAC-seq).
- 集成的snATAC-seq数据与来自206个样本的匹配单细胞或单核RNA测序 (sc/snRNA-seq) 数据.
- 分析了超过一百万个细胞以识别可访问的染色体区域,转录因子动机和规律.
主要成果:
- 确定了常见和癌症特异性的表观遗传驱动因素 (例如,ABCC1,VEGFA,GATA6,FOX家族动机,FGF19,ASAP2,EN1,PBX3动机).
- 与TP53,缺氧和TNF信号传递相关的特定途径.
- 相关的雌激素反应,上皮介质转变,以及转移的顶端结路.
- 揭示了增强剂可访问性和基因表达,以及表观遗传和遗传驱动因素之间的强烈相关性.
结论:
- 构建的地图集为研究癌症的表观遗传动态提供了基础.
- 表观遗传驱动因素在癌症发病,进展和转移中起着重要作用.
- 了解表观遗传和遗传因素之间的相互作用对于癌症研究至关重要.
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