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

被引：666

作者：

Darmanis, Spyros ^{[1
,2
,3
]}

Sloan, Steven A. ^{[4
]}

Croote, Derek ^{[1
,2
,3
]}

Mignardi, Marco ^{[1
,2
,3
]}

Chernikova, Sophia ^{[5
]}

Samghababi, Peyman ^{[6
]}

Zhang, Ye ^{[4
]}

Neff, Norma ^{[1
,2
,3
]}

Kowarsky, Mark ^{[1
,2
,3
]}

Caneda, Christine ^{[4
]}

Li, Gordon ^{[5
]}

Chang, Steven D. ^{[5
]}

Connolly, Ian David ^{[5
]}

Li, Yingmei ^{[5
]}

Barres, Ben A. ^{[4
]}

Gephart, Melanie Hayden ^{[5
]}

Quake, Stephen R. ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Dept Bioengn, 318 Campus Dr, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Appl Phys, 318 Campus Dr, Stanford, CA 94305 USA

[3] Chan Zuckerberg Biohub, 318 Campus Dr, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Neurobiol, 291 Campus Dr, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Neurosurg, 300 Pasteur Dr, Stanford, CA 94304 USA

[6] Stanford Univ, Dept Pathol, 300 Pasteur Dr, Stanford, CA 94304 USA

来源：

CELL REPORTS | 2017年 / 21卷 / 05期

关键词：

EXPRESSION; REVEALS; GROWTH; GENE; HETEROGENEITY; TRANSCRIPTOME; NFIB;

D O I：

10.1016/j.celrep.2017.10.030

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1399 / 1410

页数：12

共 33 条

[1] New tools for studying microglia in the mouse and human CNS [J].

Bennett, Mariko L. ;

Bennett, F. Chris ;

Liddelow, Shane A. ;

Ajami, Bahareh ;

Zamanian, Jennifer L. ;

Fernhoff, Nathaniel B. ;

Mulinyawe, Sara B. ;

Bohlen, Christopher J. ;

Adil, Aykezar ;

Tucker, Andrew ;

Weissman, Irving L. ;

Chang, Edward F. ;

Li, Gordon ;

Grant, Gerald A. ;

Gephart, Melanie G. Hayden ;

Barres, Ben A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (12) :E1738-E1746

[2] Tumor relapse prevented by combining adoptive T cell therapy with Salmonella typhimurium [J].

Binder, David C. ;

Arina, Ainhoa ;

Wen, Frank ;

Tu, Tony ;

Zhao, Ming ;

Hoffman, Robert M. ;

Wainwright, Derek A. ;

Schreiber, Hans .

ONCOIMMUNOLOGY, 2016, 5 (06)

[3] Current and future strategies for treatment of glioma [J].

Bush, Nancy Ann Oberheim ;

Chang, Susan M. ;

Berger, Mitchel S. .

NEUROSURGICAL REVIEW, 2017, 40 (01) :1-14

[4] The transcription factor Nfix is essential for normal brain development [J].

Campbell, Christine E. ;

Piper, Michael ;

Plachez, Celine ;

Yeh, Yu-Ting ;

Baizer, Joan S. ;

Osinski, Jason M. ;

Litwack, E. David ;

Richards, Linda J. ;

Gronostajski, Richard M. .

BMC DEVELOPMENTAL BIOLOGY, 2008, 8

[5] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[6] Diffuse glioma growth: a guerilla war [J].

Claes, An ;

Idema, Albert J. ;

Wesseling, Pieter .

ACTA NEUROPATHOLOGICA, 2007, 114 (05) :443-458

[7] A survey of human brain transcriptome diversity at the single cell level [J].

Darmanis, Spyros ;

Sloan, Steven A. ;

Zhang, Ye ;

Enge, Martin ;

Caneda, Christine ;

Shuer, Lawrence M. ;

Gephart, Melanie G. Hayden ;

Barres, Ben A. ;

Quake, Stephen R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (23) :7285-7290

[8] Molecular mechanisms of glioma cell migration and invasion [J].

Demuth, T ;

Berens, ME .

JOURNAL OF NEURO-ONCOLOGY, 2004, 70 (02) :217-228

[9] Nfib Promotes Metastasis through a Widespread Increase in Chromatin Accessibility [J].

Denny, Sarah K. ;

Yang, Dian ;

Chuang, Chen-Hua ;

Brady, Jennifer J. ;

Lim, Jing Shan ;

Gruner, Barbara M. ;

Chiou, Shin-Heng ;

Schep, Alicia N. ;

Baral, Jessika ;

Hamard, Cecile ;

Antoine, Martine ;

Wislez, Marie ;

Kong, Christina S. ;

Connolly, Andrew J. ;

Park, Kwon-Sik ;

Sage, Julien ;

Greenleaf, William J. ;

Winslow, Monte M. .

CELL, 2016, 166 (02) :328-342

[10]

Fan J, 2016, NAT METHODS, V13, P241, DOI [10.1038/NMETH.3734, 10.1038/nmeth.3734]

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