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

被引：491

作者：

Filbin, Mariella G. ^{[1
,2
,3
,4
,5
,6
,7
]}

Tirosh, Itay ^{[5
,6
,8
]}

Hovestadt, Volker ^{[1
,2
,3
,5
,6
]}

Shaw, McKenzie L. ^{[1
,2
,3
,5
,6
]}

Escalante, Leah E. ^{[1
,2
,3
,5
,6
]}

Mathewson, Nathan D. ^{[3
,9
]}

Neftel, Cyril ^{[1
,2
,3
,5
,6
,10
]}

Frank, Nelli ^{[11
]}

Pelton, Kristine ^{[12
]}

Hebert, ChristineM. ^{[1
,2
,3
,5
,6
]}

Haberler, Christine ^{[13
]}

Yizhak, Keren ^{[6
]}

Gojo, Johannes ^{[7
]}

Egervari, Kristof ^{[1
,2
,3
]}

Mount, Christopher ^{[14
,15
,16
]}

van Galen, Peter ^{[1
,2
,3
,5
,6
]}

Bonal, Dennis M. ^{[17
]}

Quang-De Nguyen ^{[17
]}

Beck, Alexander ^{[1
,2
,3
]}

Sinai, Claire ^{[4
,12
]}

Czech, Thomas ^{[18
]}

Dorfer, Christian ^{[18
]}

Goumnerova, Liliana ^{[4
]}

Lavarino, Cinzia ^{[19
]}

Carcaboso, Angel M. ^{[19
]}

Mora, Jaume ^{[19
]}

Mylvaganam, Ravindra ^{[1
,2
,3
]}

Luo, Christina C. ^{[1
,2
,3
]}

Peyrl, Andreas ^{[7
]}

Popovic, Mara ^{[20
]}

Azizi, Amedeo

Batchelor, Tracy T. ^{[21
,22
]}

Frosch, Matthew P. ^{[1
,2
,3
]}

Martinez-Lage, Maria ^{[1
,2
,3
]}

Kieran, Mark W. ^{[4
]}

Bandopadhayay, Pratiti ^{[4
,6
]}

Beroukhim, Rameen ^{[3
,23
,24
]}

Fritsch, Gerhard ^{[11
]}

Getz, Gad ^{[1
,3
,6
]}

Rozenblatt-Rosen, Orit ^{[5
,6
]}

Wucherpfennig, Kai W. ^{[3
,9
]}

Louis, David N. ^{[1
,2
,3
]}

Monje, Michelle ^{[14
,15
,16
]}

Slavc, Irene ^{[7
]}

Ligon, Keith L. ^{[4
,6
,12
]}

Golub, Todd R. ^{[4
,6
]}

Regev, Aviv ^{[5
,6
,25
]}

Bernstein, Bradley E. ^{[1
,2
,3
,5
,6
]}

Suva, Mario L. ^{[1
,2
,3
,5
,6
]}

机构：

[1] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[3] Harvard Med Sch, Boston, MA 02114 USA

[4] Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Oncol, Boston, MA 02215 USA

[5] Broad Inst Harvard & Massachussetts Inst Technol, Klarman Cell Observ, Cambridge, MA 02142 USA

[6] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[7] Med Univ Vienna, Dept Pediat & Adolescent Med, Vienna, Austria

[8] Weizmann Inst Sci, Dept Mol Cell Biol, IL-7610001 Rehovot, Israel

[9] Dana Farber Canc Inst, Dept Neurol, Dept Microbiol & Immunobiol, Dept Canc Immunol & Virol, Boston, MA 02215 USA

[10] CHU Vaudois, Fac Biol & Med, Inst Pathol, CH-1011 Lausanne, Switzerland

[11] Med Univ Vienna, St Anna Kinderspital, CCRI, Vienna, Austria

[12] Boston Childrens Hosp, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Oncol Pathol, Boston, MA 02215 USA

[13] Med Univ Vienna, Inst Neurol, Vienna, Austria

[14] Stanford Univ, Dept Neurol, Sch Med, Stanford, CA 94305 USA

[15] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA

[16] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[17] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Ctr Biomed Imaging Oncol, Boston, MA 02215 USA

[18] Med Univ Vienna, Dept Neurosurg, Vienna, Austria

[19] Hosp St Joan Deu, Dev Tumor Biol Lab, Barcelona 08950, Spain

[20] Univ Ljubljana, Inst Pathol, Fac Med, Ljubljana, Slovenia

[21] Harvard Med Sch, Massachusetts Gen Hosp, Canc Ctr, Div Hematol Oncol,Dept Neurol, Boston, MA USA

[22] Harvard Med Sch, Massachusetts Gen Hosp, Canc Ctr, Div Hematol Oncol,Dept Radiat Oncol, Boston, MA USA

[23] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[24] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA

[25] MIT, Howard Hughes Med Inst, Koch Inst Integrat Canc Res, Dept Biol, Cambridge, MA 02139 USA

来源：

SCIENCE | 2018年 / 360卷 / 6386期

关键词：

STEM-CELLS; GLIOBLASTOMA; HETEROGENEITY; MUTATION; MOUSE;

D O I：

10.1126/science.aao4750

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：331 / 335

页数：5

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