描述与乳腺癌相关的基因调控程序中的异质 cis 调控元素
Chisa Hori1,2, Kohei Kumegawa3, Sumito Saeki1,4
1Division of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Genome medicine
|November 27, 2025
概括
这项研究揭示了 cis 调节元素 (CRE) 异质性驱动乳腺癌 (BC) 多样性. 单细胞表观基因组测绘了这些CREs,揭示了它们在瘤内和瘤间变异中的作用.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 细胞调节元件 (CREs) 对瘤基因表达和癌症表型至关重要.
- 瘤异质性是癌症的一个关键挑战,与CRE变异有关.
- 与癌症相关的CREs的特征是复杂的,需要先进的分析方法.
研究的目的:
- 绘制乳腺癌 (BC) 多细胞生态系统的地图.
- 确定与BC.相关的候选cis调节元件 (cCREs).
- 研究CRE异质性在瘤内和瘤间多样性中的作用.
主要方法:
- 在38个临床乳腺癌样本上进行了转化酶可访问染色质的单细胞测定与测序 (scATAC-seq).
- 利用标记基因可访问性和单细胞RNA测序集成用于细胞注释.
- 确定了差异可访问的cCREs (DA-cCREs) 并构建了增强器-促进器网络.
主要成果:
- 从乳腺癌样本中的22,775个单细胞中分析了染色质可访问性.
- 在BC生态系统中确定了224,585个候选ciss-regulatory元素 (cCREs).
- 证明增强剂的可访问性在瘤内和瘤之间有所不同,显示出显著的监管异质性.
结论:
- 这项研究为未来乳腺癌表观遗传学研究提供了有价值的数据集.
- 这些发现突显了瘤内部和瘤之间多样化的cis-regulatory景观.
- cis调节元件 (CREs) 被认为是乳腺癌中瘤内部和瘤间异质性的关键调节者.
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