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通过单细胞RNA-seq剖析的H3K27M质瘤的发育和致癌方案

Mariella G Filbin^1,2,3,4,5, Itay Tirosh^3,4,6, Volker Hovestadt^1,3,4

¹Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Science (New York, N.Y.)

|April 21, 2018

概括

基因组H3 lysine27-to-methionine突变 (H3K27M) 驱动儿科中线质瘤,这些质瘤主要由类似于寡细胞的前体细胞组成. 这些细胞表现出更高的增殖和瘤扩散潜力,表明PDGFRA信号作为治疗点.

科学领域:

儿童神经瘤学
癌细胞生物学
发展神经生物学

背景情况:

H3K27M - 瘤是侵袭性的小儿脑瘤,主要影响中枢神经系统的中间线.
虽然已知遗传驱动因素,但细胞组成和瘤结构仍不明确.
了解细胞背景对于H3K27M瘤的产生至关重要.

研究的目的:

在单细胞分辨率下描述H3K27M结质瘤的细胞结构.
识别不同的细胞群和它们在瘤进展中的作用.
根据细胞和分子概况探索潜在的治疗点.

主要方法:

单细胞RNA测序 (scRNA-seq) 在6个主要H3K27M瘤样本和匹配模型中的3321个细胞上进行.
使用生物信息分析来识别细胞类型,状态和信号通路.
对基因子克隆进行了比较分析.

主要成果:

H3K27M结质瘤主要由类似于寡细胞前体 (OPC) 的细胞组成,差异化恶性细胞较少.
与差异化细胞相比,OPC类细胞表现出增强的增殖和瘤扩散能力.
确定PDGFRA信号传递是维持OPC类细胞群的关键途径.

结论:

H3K27M质瘤细胞组成主要由具有高瘤扩散潜力的OPC类细胞组成.
在这些瘤中以单细胞分辨率运行瘤和发育程序.
针对PDGFRA信号可能为H3K27M瘤提供治疗策略.

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