Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma
Spyros Darmanis,
Steven A. Sloan,
Derek Croote,
Marco Mignardi,
Sophia Chernikova,
Peyman Samghababi,
Ye Zhang,
Norma Neff,
Mark Kowarsky,
Christine Caneda,
Gordon Li,
Steven D. Chang,
Ian David Connolly,
Yingmei Li,
Ben A. Barres,
Melanie Hayden Gephart,
Stephen R. Quake
Affiliations
Spyros Darmanis
Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA
Steven A. Sloan
Department of Neurobiology, Stanford University, 291 Campus Drive, Stanford, CA 94305, USA
Derek Croote
Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA
Marco Mignardi
Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA
Sophia Chernikova
Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA
Peyman Samghababi
Department of Pathology, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA
Ye Zhang
Department of Neurobiology, Stanford University, 291 Campus Drive, Stanford, CA 94305, USA
Norma Neff
Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA
Mark Kowarsky
Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA
Christine Caneda
Department of Neurobiology, Stanford University, 291 Campus Drive, Stanford, CA 94305, USA
Gordon Li
Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA
Steven D. Chang
Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA
Ian David Connolly
Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA
Yingmei Li
Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA
Ben A. Barres
Department of Neurobiology, Stanford University, 291 Campus Drive, Stanford, CA 94305, USA
Melanie Hayden Gephart
Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA
Stephen R. Quake
Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA; Corresponding author
Summary: 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. : 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. Keywords: single cell, RNA-seq, glioma, glioblastoma, GBM, brain, heterogeneity, infiltrating, diffuse, checkpoint
