在三阴性乳腺癌中药物诱导的转录基因重编程的单细胞解码
Farhia Kabeer1,2, Hoa Tran2, Mirela Andronescu1,2
1Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Genome biology
|July 18, 2024
概括
具有强烈的抗性的乳腺癌克隆显示固定基因型和最小的转录变化. 较弱的克隆表现出动态的,非基因组的可塑性,有助于抗性.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 文字转录学 (Transcriptomics) 是一个学科.
背景情况:
- 乳腺癌中的细胞内在耐药性涉及基因组和非基因组变异.
- 身体拷贝数 (CN) 的变化驱动着转录性变化和化疗耐药性.
- 从转录和基因组数据中准确估计克隆适应性至关重要.
研究的目的:
- 鉴定三阴性乳腺癌 (TNBC) 中药物相关转录细胞状态的基因组和转录组机制.
- 在暴露下分析TNBC瘤中的克隆反应和转录可塑性.
主要方法:
- 利用来自TNBC患者衍生异种移植 (PDX) 实验的时间序列单细胞RNA测序 (scRNA-seq) 数据.
- 同时测量单细胞CN数据与转录基因数据.
- 进行路径分析和伪时间分析以了解转录动态.
主要成果:
- 在暴露于金的TNBC瘤中观察到明显的克隆反应,高适应性克隆接受了扫描,低适应性克隆显示动态转录.
- 确定了表皮质-介质细胞过渡和细胞因子信号通路作为抵抗的关键.
- 伪物体分析显示转录逆转中的歇斯底里,表明在暴露时出现了新的中间状态.
结论:
- 在金下,强烈适合的克隆保持了固定的基因型,最大限度地减少了转录逆转.
- 较弱的克隆显示非基因组转录性可塑性,有助于白金耐药性.
- 无论是与CN相关的还是与CN独立的机制都会影响的耐药性,影响治疗策略.
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