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科学家绘制胶质母细胞瘤蓝图
来源:小柯机器人 发布时间:2019/8/10 21:45:20

美国麻省总医院的Mario L. Suvà研究组和以色列魏茨曼科学研究所的Itay Tirosh研究组合作描绘了包含细胞状态、可塑性及遗传的胶质母细胞瘤蓝图。2019年8月9日出版的《细胞》发表了这项成果。

研究人员使用一个整合多种信息的方法得到了胶质母细胞瘤细胞状态和遗传多样性的统一模型,这些信息包括来自28个肿瘤的单细胞RNA测序、来自癌症基因组图谱(TCGA)的401个样本的大量遗传和表达分析、功能验证以及单细胞谱系追踪。研究人员发现胶质母细胞瘤中的恶性细胞存在四种主要的细胞状态,这些状态代表不同的神经细胞类型;此外这些恶性细胞受肿瘤微环境的影响,并表现出可塑性。每种状态细胞的相对频率在胶质母细胞瘤样品之间变化,并受CDK4、EGFR和PDGFRA基因座的拷贝数扩增以及NF1基因座的突变影响,这些突变均有利于确定其状态。这些工作为胶质母细胞瘤提供了一个整合恶性细胞程序、细胞可塑性以及驱动基因调控的蓝图

据了解,胶质母细胞瘤是一种无法治愈且对其了解不多的肿瘤,其遗传、表观遗传和发育程序的多样性导致了这种肿瘤的发生,但对其精确的描绘仍然具有挑战性。



附:英文原文

Title: An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma

Author: Cyril Neftel, Julie Laffy, Mariella G. Filbin, Bradley E. Bernstein, Itay Tirosh, Mario L. Suvà

Issue&Volume: Volume 178 Issue 4

Abstract: Diverse genetic, epigenetic, and developmental programs drive glioblastoma, an incurable and poorly understood tumor, but their precise characterization remains challenging. Here, we use an integrative approach spanning single-cell RNA-sequencing of 28 tumors, bulk genetic and expression analysis of 401 specimens from the The Cancer Genome Atlas (TCGA), functional approaches, and single-cell lineage tracing to derive a unified model of cellular states and genetic diversity in glioblastoma. We find that malignant cells in glioblastoma exist in four main cellular states that recapitulate distinct neural cell types, are influenced by the tumor microenvironment, and exhibit plasticity. The relative frequency of cells in each state varies between glioblastoma samples and is influenced by copy number amplifications of the CDK4, EGFR, and PDGFRA loci and by mutations in the NF1 locus, which each favor a defined state. Our work provides a blueprint for glioblastoma, integrating the malignant cell programs, their plasticity, and their modulation by genetic drivers.

DOI: https://doi.org/10.1016/j.cell.2019.06.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30687-7

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/

本期文章:《细胞》:Volume 178 Issue 4