Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma
Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma
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DOI：
10.1016/j.celrep.2017.10.030
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发表时间：
2017-10-31
期刊：
影响因子：
8.8
通讯作者：
Quake, Stephen R.
中科院分区：
文献类型：
--
作者：
Darmanis, Spyros;Sloan, Steven A.;Quake, Stephen R.
胶质母细胞瘤（GBM）是成人中最常见的原发性脑癌，并且由于其扩散性质而难以治疗。我们对4名患者的3，589个细胞进行了单细胞RNA测序（RNA-seq）。我们从肿瘤中心以及周围组织中获得细胞。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边区域的浸润性肿瘤细胞。尽管肿瘤细胞之间存在显著的异质性，我们发现浸润性GBM细胞在患者之间共享一致的基因签名，这表明了共同的浸润机制。此外，在研究对肿瘤的免疫应答时，我们发现转录上不同的髓样细胞群驻留在肿瘤核心和周围的瘤周空间中。我们的数据提供了GBM细胞类型的详细解剖，揭示了有关肿瘤形成和迁移的丰富信息。
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.