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

• Published in: Cell reports (Cambridge) Vol. 21; no. 5; pp. 1399 - 1410
• Main Authors: Darmanis, Spyros, Sloan, Steven A., Croote, Derek, Mignardi, Marco, Chernikova, Sophia, Samghababi, Peyman, Zhang, Ye, Neff, Norma, Kowarsky, Mark, Caneda, Christine, Li, Gordon, Chang, Steven D., Connolly, Ian David, Li, Yingmei, Barres, Ben A., Gephart, Melanie Hayden, Quake, Stephen R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.10.2017; Elsevier
• Subjects: brain; checkpoint; diffuse; GBM; glioblastoma; glioma; heterogeneity; infiltrating; RNA-seq; single cell; infiltrating; checkpoint; single cell; glioblastoma; GBM; RNA-seq; glioma; diffuse; brain; heterogeneity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.10.030

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. [Display omitted] •Vast genomic and transcriptomic heterogeneity of GBM tumor cells•Characterization of individual GBM infiltrating cells in peritumoral tissue•Possible convergent strategy of infiltration between highly variable tumors•Myeloid cells participate in enhancing tumor growth, survival, and dissemination Darmanis et al. perform single-cell transcriptomic analyses of neoplastic and stromal cells within and proximal to primary glioblastomas. The authors describe a population of neoplastic-infiltrating glioblastoma cells as well as a putative role of tumor-infiltrating immune cells in supporting tumor growth.