PMID- 29091775 OWN - NLM STAT- MEDLINE DCOM- 20180612 LR - 20181113 IS - 2211-1247 (Electronic) VI - 21 IP - 5 DP - 2017 Oct 31 TI - Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma. PG - 1399-1410 LID - S2211-1247(17)31462-6 [pii] LID - 10.1016/j.celrep.2017.10.030 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved FAU - Darmanis, Spyros AU - Darmanis S AD - Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA. FAU - Sloan, Steven A AU - Sloan SA AD - Department of Neurobiology, Stanford University, 291 Campus Drive, Stanford, CA 94305, USA. FAU - Croote, Derek AU - Croote D AD - Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA. FAU - Mignardi, Marco AU - Mignardi M AD - Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA. FAU - Chernikova, Sophia AU - Chernikova S AD - Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA. FAU - Samghababi, Peyman AU - Samghababi P AD - Department of Pathology, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA. FAU - Zhang, Ye AU - Zhang Y AD - Department of Neurobiology, Stanford University, 291 Campus Drive, Stanford, CA 94305, USA. FAU - Neff, Norma AU - Neff N AD - Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA. FAU - Kowarsky, Mark AU - Kowarsky M AD - Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA. FAU - Caneda, Christine AU - Caneda C AD - Department of Neurobiology, Stanford University, 291 Campus Drive, Stanford, CA 94305, USA. FAU - Li, Gordon AU - Li G AD - Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA. FAU - Chang, Steven D AU - Chang SD AD - Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA. FAU - Connolly, Ian David AU - Connolly ID AD - Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA. FAU - Li, Yingmei AU - Li Y AD - Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA. FAU - Barres, Ben A AU - Barres BA AD - Department of Neurobiology, Stanford University, 291 Campus Drive, Stanford, CA 94305, USA. FAU - Gephart, Melanie Hayden AU - Gephart MH AD - Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94304, USA. FAU - Quake, Stephen R AU - Quake SR AD - Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, 318 Campus Drive, Stanford, CA 94305, USA. Electronic address: quake@stanford.edu. LA - eng GR - R01 NS081703/NS/NINDS NIH HHS/United States GR - T32 GM007365/GM/NIGMS NIH HHS/United States GR - F30 MH106261/MH/NIMH NIH HHS/United States GR - R01 CA216054/CA/NCI NIH HHS/United States GR - R00 NS089780/NS/NINDS NIH HHS/United States GR - R21 CA193046/CA/NCI NIH HHS/United States GR - R01 MH099555/MH/NIMH NIH HHS/United States PT - Journal Article PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 RN - 0 (RNA, Neoplasm) SB - IM MH - Brain Neoplasms/genetics/metabolism/*pathology MH - Cluster Analysis MH - DNA Copy Number Variations MH - Glioblastoma/genetics/metabolism/*pathology MH - Humans MH - Magnetic Resonance Imaging MH - RNA, Neoplasm/chemistry/isolation & purification/*metabolism MH - Sequence Analysis, RNA MH - Single-Cell Analysis PMC - PMC5810554 MID - NIHMS938967 OTO - NOTNLM OT - GBM OT - RNA-seq OT - brain OT - checkpoint OT - diffuse OT - glioblastoma OT - glioma OT - heterogeneity OT - infiltrating OT - single cell EDAT- 2017/11/02 06:00 MHDA- 2018/06/13 06:00 PMCR- 2018/02/13 CRDT- 2017/11/02 06:00 PHST- 2017/02/23 00:00 [received] PHST- 2017/07/19 00:00 [revised] PHST- 2017/10/08 00:00 [accepted] PHST- 2017/11/02 06:00 [entrez] PHST- 2017/11/02 06:00 [pubmed] PHST- 2018/06/13 06:00 [medline] PHST- 2018/02/13 00:00 [pmc-release] AID - S2211-1247(17)31462-6 [pii] AID - 10.1016/j.celrep.2017.10.030 [doi] PST - ppublish SO - Cell Rep. 2017 Oct 31;21(5):1399-1410. doi: 10.1016/j.celrep.2017.10.030.