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单细胞 RNA 测序分析人类脑胶质瘤迁移前沿浸润性肿瘤细胞。

Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma.

机构信息

Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA.

Department of Neurobiology, Stanford University, 291 Campus Drive, Stanford, CA 94305, USA.

出版信息

Cell Rep. 2017 Oct 31;21(5):1399-1410. doi: 10.1016/j.celrep.2017.10.030.

Abstract

Glioblastoma (GBM) is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq) on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor's genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration.

摘要

胶质母细胞瘤(GBM)是成人中最常见的原发性脑癌,由于其弥漫性,治疗极为困难。我们对来自四名患者的一个队列中的 3589 个细胞进行了单细胞 RNA 测序(RNA-seq)。我们从肿瘤核心区域以及周围的外围组织中获取了细胞。我们的分析揭示了肿瘤基因组和转录组的细胞变异。我们还能够识别出核心病变周围区域的浸润性肿瘤细胞。尽管肿瘤细胞之间存在明显的异质性,但我们发现浸润性 GBM 细胞在患者之间共享一致的基因特征,这表明浸润存在共同的机制。此外,在研究肿瘤的免疫反应时,我们发现转录上不同的髓样细胞群存在于肿瘤核心和周围肿瘤空间中。我们的数据提供了对 GBM 细胞类型的详细剖析,揭示了有关肿瘤形成和迁移的大量信息。

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