单细胞多组学揭示了肝细胞母细胞瘤中克隆进化和细胞可塑性的相互作用
Amélie Roehrig1, Theo Z Hirsch1, Aurore Pire1
1Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, INSERM, Paris, France.
Nature communications
|April 8, 2024
概括
肝母细胞瘤细胞表现出不同的状态,从肝脏前代细胞到介质细胞. 遗传变化和表观遗传可塑性影响瘤细胞对化疗的反应.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 肝母细胞瘤 (HB) 呈现细胞异质性,影响患者的治疗结果.
- 驱动HB细胞可塑性的机制在很大程度上是未知的.
研究的目的:
- 研究肝细胞母细胞瘤细胞可塑性的分子驱动因素.
- 了解HB.的克隆进化和表观遗传调节之间的相互作用.
主要方法:
- 采用单细胞多原子策略来分析HB.
- 利用空间转录学来绘制细胞状态和染色质可访问性来定义调节网络.
- 对体质变化的单细胞映射确定了瘤的克隆架构.
主要成果:
- 在HB中确定了一种细胞连续,从肝细胞到介质细胞状态,具有中间的祖先种群.
- 定义了基因调节网络和细胞状态转换的转录因子动态.
- 发现个体基因亚克隆具有不同的细胞可塑性范围.
- 发现,具有高干细胞和DNA修复基因表达的肝脏前代类子克隆在化疗后更快地增殖.
结论:
- 这项研究揭示了克隆进化和表观遗传可塑性如何共同塑造肝细胞瘤亚克隆对治疗的反应.
- 了解这些机制对于开发向性肝细胞母细胞瘤治疗至关重要.
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