活性髓母细胞瘤增强剂显示出特定亚群的细胞起源
Charles Y Lin1, Serap Erkek2,3, Yiai Tong4
1Medical Oncology, Dana Farber Cancer Institute (DFCI), Boston, Massachusetts 02215, USA.
Nature
|January 28, 2016
概括
这项研究绘制了脑髓母细胞瘤的调节元素,揭示了驱动子组分离的关键转录因子,并提供了对这种儿童脑瘤起源的见解.
科学领域:
- 基因组学
- 表观遗传学
- 发育生物学
背景情况:
- 骨髓母细胞瘤是一种具有四个不同的分子子组的恶性儿童脑瘤.
- 了解这些子组的监管回路和发展起源至关重要.
研究的目的:
- 描述脑髓母细胞瘤子组的活跃 cis 调节场景.
- 确定驱动子组分离的转录因子及其来源细胞.
主要方法:
- 染色体免疫沉,然后对H3K27ac和BRD4进行测序 (ChIP-seq).
- 组织匹配的DNA甲基化和转录组数据的分析.
- 核心调节电路的计算重建.
主要成果:
- 在28个原发性脑髓母细胞瘤样本中详细分析了活跃的Cis调节场景.
- 鉴定不同调节的增强剂和超级增强剂,突出显示子组异质性.
- 负责分组分歧的转录因子总套已被确定并验证.
- 这涉及4组髓母细胞的候选细胞.
结论:
- 综合分析提供了关于脑髓母细胞瘤的调节结构和未被识别的依赖性的见解.
- 这项研究有助于进一步了解骨髓母细胞瘤的异质性和细胞起源.
- 这些发现为脑髓母细胞瘤生物学提供了新的,临床相关的见解.
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