Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq

Andrew S. Venteicher; Itay Tirosh; Christine Hebert; Keren Yizhak; Cyril Neftel; Mariella G. Filbin; Volker Hovestadt; Leah E. Escalante; McKenzie L. Shaw; Christopher Rodman; Shawn M. Gillespie; Danielle Dionne; Christina C. Luo; Hiranmayi Ravichandran; Ravindra Mylvaganam; Christopher Mount; Maristela L. Onozato; Brian V. Nahed; Hiroaki Wakimoto; William T. Curry; A. John Iafrate; Miguel N. Rivera; Matthew P. Frosch; Todd R. Golub; Priscilla K. Brastianos; Gad Getz; Anoop P. Patel; Michelle Monje; Daniel P. Cahill; Orit Rozenblatt-Rosen; David N. Louis; Bradley E. Bernstein; Aviv Regev; Mario L. Suvà

doi:10.1126/science.aai8478

Research Article

Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq

Andrew S. Venteicher¹,²,³,*,
Itay Tirosh²,*,†,
Christine Hebert¹,²,
Keren Yizhak¹,²,
Cyril Neftel¹,²,⁴,
Mariella G. Filbin¹,²,⁵,
Volker Hovestadt¹,²,
Leah E. Escalante¹,²,
McKenzie L. Shaw¹,²,
Christopher Rodman²,
Shawn M. Gillespie¹,
Danielle Dionne²,
Christina C. Luo¹,
Hiranmayi Ravichandran¹,
Ravindra Mylvaganam¹,
Christopher Mount⁶,
Maristela L. Onozato¹,
Brian V. Nahed³,
Hiroaki Wakimoto³,
William T. Curry³,
A. John Iafrate¹,
Miguel N. Rivera¹,²,
Matthew P. Frosch¹,
Todd R. Golub²,⁵,⁷,
Priscilla K. Brastianos⁸,
Gad Getz¹,²,
Anoop P. Patel³,
Michelle Monje⁶,
Daniel P. Cahill³,
Orit Rozenblatt-Rosen²,
David N. Louis¹,
Bradley E. Bernstein¹,²,
Aviv Regev²,⁷,⁹,†,‡,
Mario L. Suvà¹,²,†,‡

¹Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
²Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
³Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁴Institute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
⁵Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children’s Hospital Cancer Center, Boston, MA 02215, USA.
⁶Departments of Neurology, Neurosurgery, Pediatrics and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁷Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
⁸Departments of Medicine and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁹Koch Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

↵†Corresponding author. Email: suva.mario{at}mgh.harvard.edu (M.L.S.); aregev{at}broadinstitute.org (A.R.); tirosh{at}broadinstitute.org (I.T.)

↵* These authors contributed equally to this work.
↵‡ These authors contributed equally to this work.

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Science 31 Mar 2017:
Vol. 355, Issue 6332, eaai8478
DOI: 10.1126/science.aai8478

Andrew S. Venteicher

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Itay Tirosh

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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For correspondence: suva.mario@mgh.harvard.edu aregev@broadinstitute.org tirosh@broadinstitute.org

Christine Hebert

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Keren Yizhak

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Cyril Neftel

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.Institute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.

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Mariella G. Filbin

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children’s Hospital Cancer Center, Boston, MA 02215, USA.

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Volker Hovestadt

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Leah E. Escalante

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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McKenzie L. Shaw

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Christopher Rodman

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Shawn M. Gillespie

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Danielle Dionne

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Christina C. Luo

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Hiranmayi Ravichandran

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Ravindra Mylvaganam

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Christopher Mount

Departments of Neurology, Neurosurgery, Pediatrics and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

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Maristela L. Onozato

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Brian V. Nahed

Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Hiroaki Wakimoto

Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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William T. Curry

Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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A. John Iafrate

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Miguel N. Rivera

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Matthew P. Frosch

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Todd R. Golub

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children’s Hospital Cancer Center, Boston, MA 02215, USA.Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

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Priscilla K. Brastianos

Departments of Medicine and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Gad Getz

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Anoop P. Patel

Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Michelle Monje

Departments of Neurology, Neurosurgery, Pediatrics and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

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Daniel P. Cahill

Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Orit Rozenblatt-Rosen

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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David N. Louis

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Bradley E. Bernstein

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Aviv Regev

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.Koch Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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For correspondence: suva.mario@mgh.harvard.edu aregev@broadinstitute.org tirosh@broadinstitute.org

Mario L. Suvà

Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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For correspondence: suva.mario@mgh.harvard.edu aregev@broadinstitute.org tirosh@broadinstitute.org

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Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq

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