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

View ORCID ProfileAndrew S. Venteicher¹,²,³,*,
View ORCID ProfileItay Tirosh²,*,†,
Christine Hebert¹,²,
Keren Yizhak¹,²,
View ORCID ProfileCyril Neftel¹,²,⁴,
Mariella G. Filbin¹,²,⁵,
Volker Hovestadt¹,²,
Leah E. Escalante¹,²,
McKenzie L. Shaw¹,²,
Christopher Rodman²,
View ORCID ProfileShawn M. Gillespie¹,
Danielle Dionne²,
View ORCID ProfileChristina C. Luo¹,
Hiranmayi Ravichandran¹,
View ORCID ProfileRavindra Mylvaganam¹,
Christopher Mount⁶,
Maristela L. Onozato¹,
Brian V. Nahed³,
Hiroaki Wakimoto³,
William T. Curry³,
A. John Iafrate¹,
Miguel N. Rivera¹,²,
Matthew P. Frosch¹,
View ORCID ProfileTodd R. Golub²,⁵,⁷,
Priscilla K. Brastianos⁸,
View ORCID ProfileGad Getz¹,²,
View ORCID ProfileAnoop P. Patel³,
Michelle Monje⁶,
View ORCID ProfileDaniel P. Cahill³,
Orit Rozenblatt-Rosen²,
View ORCID ProfileDavid N. Louis¹,
View ORCID ProfileBradley E. Bernstein¹,²,
View ORCID ProfileAviv Regev²,⁷,⁹,†,‡,
View ORCID ProfileMario 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

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.

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ORCID record for Andrew S. Venteicher

Itay Tirosh

2Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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ORCID record for Itay Tirosh
For correspondence: suva.mario@mgh.harvard.edu aregev@broadinstitute.org tirosh@broadinstitute.org

Christine Hebert

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.

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Keren Yizhak

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.

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Cyril Neftel

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.

4Institute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.

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Mariella G. Filbin

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.

5Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children’s Hospital Cancer Center, Boston, MA 02215, USA.

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Volker Hovestadt

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.

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Leah E. Escalante

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.

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McKenzie L. Shaw

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.

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Christopher Rodman

2Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Shawn M. Gillespie

1Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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ORCID record for Shawn M. Gillespie

Danielle Dionne

2Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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Christina C. Luo

1Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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ORCID record for Christina C. Luo

Hiranmayi Ravichandran

1Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Ravindra Mylvaganam

1Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Christopher Mount

6Departments of Neurology, Neurosurgery, Pediatrics and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

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Maristela L. Onozato

1Department 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

3Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Hiroaki Wakimoto

3Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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William T. Curry

3Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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A. John Iafrate

1Department 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

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.

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Matthew P. Frosch

1Department 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

2Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

5Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children’s Hospital Cancer Center, Boston, MA 02215, USA.

7Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

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Priscilla K. Brastianos

8Departments of Medicine and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Gad Getz

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.

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Anoop P. Patel

3Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Michelle Monje

6Departments of Neurology, Neurosurgery, Pediatrics and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

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Daniel P. Cahill

3Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Orit Rozenblatt-Rosen

2Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

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David N. Louis

1Department 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

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.

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Aviv Regev

2Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

7Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

9Koch 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

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.

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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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