Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq

Mariella G. Filbin; Itay Tirosh; Volker Hovestadt; McKenzie L. Shaw; Leah E. Escalante; Nathan D. Mathewson; Cyril Neftel; Nelli Frank; Kristine Pelton; Christine M. Hebert; Christine Haberler; Keren Yizhak; Johannes Gojo; Kristof Egervari; Christopher Mount; Peter Van Galen; Dennis M. Bonal; Quang De Nguyen; Alexander Beck; Claire Sinai; Thomas Czech; Christian Dorfer; Liliana Goumnerova; Cinzia Lavarino; Angel M. Carcaboso; Jaume Mora; Ravindra Mylvaganam; Christina C. Luo; Andreas Peyrl; Mara Popović; Amedeo Azizi; Tracy T. Batchelor; Matthew P. Frosch; Maria Martinez-Lage; Mark W. Kieran; Pratiti Bandopadhayay; Rameen Beroukhim; Gerhard Fritsch; Gad Getz; Orit Rozenblatt-Rosen; Kai W. Wucherpfennig; David N. Louis; Michelle Monje; Irene Slavc; Keith L. Ligon; Todd R. Golub; Aviv Regev; Bradley E. Bernstein; Mario L. Suvà

doi:10.1126/science.aao4750

Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq

Mariella G. Filbin, Itay Tirosh, Volker Hovestadt, McKenzie L. Shaw, Leah E. Escalante, Nathan D. Mathewson, Cyril Neftel, Nelli Frank, Kristine Pelton, Christine M. Hebert, Christine Haberler, Keren Yizhak, Johannes Gojo, Kristof Egervari, Christopher Mount, Peter Van Galen, Dennis M. Bonal, Quang De Nguyen, Alexander Beck, Claire SinaiThomas Czech, Christian Dorfer, Liliana Goumnerova, Cinzia Lavarino, Angel M. Carcaboso, Jaume Mora, Ravindra Mylvaganam, Christina C. Luo, Andreas Peyrl, Mara Popović, Amedeo Azizi, Tracy T. Batchelor, Matthew P. Frosch, Maria Martinez-Lage, Mark W. Kieran, Pratiti Bandopadhayay, Rameen Beroukhim, Gerhard Fritsch, Gad Getz, Orit Rozenblatt-Rosen, Kai W. Wucherpfennig, David N. Louis, Michelle Monje, Irene Slavc, Keith L. Ligon, Todd R. Golub, Aviv Regev, Bradley E. Bernstein, Mario L. Suvà

Research output: Contribution to journal › Article › peer-review

Abstract

Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models.We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.

Original language	English
Pages (from-to)	331-335
Number of pages	5
Journal	Science
Volume	360
Issue number	6386
DOIs	https://doi.org/10.1126/science.aao4750
State	Published - 20 Apr 2018
Externally published	Yes

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Filbin, M. G., Tirosh, I., Hovestadt, V., Shaw, M. L., Escalante, L. E., Mathewson, N. D., Neftel, C., Frank, N., Pelton, K., Hebert, C. M., Haberler, C., Yizhak, K., Gojo, J., Egervari, K., Mount, C., Van Galen, P., Bonal, D. M., Nguyen, Q. D., Beck, A., ... Suvà, M. L. (2018). Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Science, 360(6386), 331-335. https://doi.org/10.1126/science.aao4750

@article{645f5873d54b468d99268f9d0c871618,

title = "Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq",

abstract = "Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models.We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.",

author = "Filbin, {Mariella G.} and Itay Tirosh and Volker Hovestadt and Shaw, {McKenzie L.} and Escalante, {Leah E.} and Mathewson, {Nathan D.} and Cyril Neftel and Nelli Frank and Kristine Pelton and Hebert, {Christine M.} and Christine Haberler and Keren Yizhak and Johannes Gojo and Kristof Egervari and Christopher Mount and {Van Galen}, Peter and Bonal, {Dennis M.} and Nguyen, {Quang De} and Alexander Beck and Claire Sinai and Thomas Czech and Christian Dorfer and Liliana Goumnerova and Cinzia Lavarino and Carcaboso, {Angel M.} and Jaume Mora and Ravindra Mylvaganam and Luo, {Christina C.} and Andreas Peyrl and Mara Popovi{\'c} and Amedeo Azizi and Batchelor, {Tracy T.} and Frosch, {Matthew P.} and Maria Martinez-Lage and Kieran, {Mark W.} and Pratiti Bandopadhayay and Rameen Beroukhim and Gerhard Fritsch and Gad Getz and Orit Rozenblatt-Rosen and Wucherpfennig, {Kai W.} and Louis, {David N.} and Michelle Monje and Irene Slavc and Ligon, {Keith L.} and Golub, {Todd R.} and Aviv Regev and Bernstein, {Bradley E.} and Suv{\`a}, {Mario L.}",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors, some rights reserved.",

year = "2018",

month = apr,

day = "20",

doi = "10.1126/science.aao4750",

language = "אנגלית",

volume = "360",

pages = "331--335",

number = "6386",

}

Filbin, MG, Tirosh, I, Hovestadt, V, Shaw, ML, Escalante, LE, Mathewson, ND, Neftel, C, Frank, N, Pelton, K, Hebert, CM, Haberler, C, Yizhak, K, Gojo, J, Egervari, K, Mount, C, Van Galen, P, Bonal, DM, Nguyen, QD, Beck, A, Sinai, C, Czech, T, Dorfer, C, Goumnerova, L, Lavarino, C, Carcaboso, AM, Mora, J, Mylvaganam, R, Luo, CC, Peyrl, A, Popović, M, Azizi, A, Batchelor, TT, Frosch, MP, Martinez-Lage, M, Kieran, MW, Bandopadhayay, P, Beroukhim, R, Fritsch, G, Getz, G, Rozenblatt-Rosen, O, Wucherpfennig, KW, Louis, DN, Monje, M, Slavc, I, Ligon, KL, Golub, TR, Regev, A, Bernstein, BE & Suvà, ML 2018, 'Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq', Science, vol. 360, no. 6386, pp. 331-335. https://doi.org/10.1126/science.aao4750

TY - JOUR

T1 - Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq

AU - Filbin, Mariella G.

AU - Tirosh, Itay

AU - Hovestadt, Volker

AU - Shaw, McKenzie L.

AU - Escalante, Leah E.

AU - Mathewson, Nathan D.

AU - Neftel, Cyril

AU - Frank, Nelli

AU - Pelton, Kristine

AU - Hebert, Christine M.

AU - Haberler, Christine

AU - Yizhak, Keren

AU - Gojo, Johannes

AU - Egervari, Kristof

AU - Mount, Christopher

AU - Van Galen, Peter

AU - Bonal, Dennis M.

AU - Nguyen, Quang De

AU - Beck, Alexander

AU - Sinai, Claire

AU - Czech, Thomas

AU - Dorfer, Christian

AU - Goumnerova, Liliana

AU - Lavarino, Cinzia

AU - Carcaboso, Angel M.

AU - Mora, Jaume

AU - Mylvaganam, Ravindra

AU - Luo, Christina C.

AU - Peyrl, Andreas

AU - Popović, Mara

AU - Azizi, Amedeo

AU - Batchelor, Tracy T.

AU - Frosch, Matthew P.

AU - Martinez-Lage, Maria

AU - Kieran, Mark W.

AU - Bandopadhayay, Pratiti

AU - Beroukhim, Rameen

AU - Fritsch, Gerhard

AU - Getz, Gad

AU - Rozenblatt-Rosen, Orit

AU - Wucherpfennig, Kai W.

AU - Louis, David N.

AU - Monje, Michelle

AU - Slavc, Irene

AU - Ligon, Keith L.

AU - Golub, Todd R.

AU - Regev, Aviv

AU - Bernstein, Bradley E.

AU - Suvà, Mario L.

PY - 2018/4/20

Y1 - 2018/4/20

N2 - Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models.We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.

AB - Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models.We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.

UR - http://www.scopus.com/inward/record.url?scp=85045656768&partnerID=8YFLogxK

U2 - 10.1126/science.aao4750

DO - 10.1126/science.aao4750

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:85045656768

SN - 0036-8075

VL - 360

SP - 331

EP - 335

JO - Science

JF - Science

IS - 6386

ER -

Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq

Abstract

ASJC Scopus subject areas

UN SDGs

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