Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.
Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.
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DOI：
10.1126/science.aao4750
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发表时间：
2018-04-20
期刊：
影响因子：
--
通讯作者：
Suvà ML
中科院分区：
文献类型：
--
作者：
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
具有组蛋白 H3 赖氨酸 27 至蛋氨酸突变的神经胶质瘤（H3K27M 神经胶质瘤）主要出现在幼儿中枢神经系统的中线，表明肿瘤发生中遗传学和细胞环境之间的合作。尽管 H3K27M 神经胶质瘤的遗传学已得到很好的表征，但其细胞结构仍然未知。我们对来自 6 个原发性 H3K27M 神经胶质瘤和匹配模型的 3321 个细胞进行了单细胞 RNA 测序。我们发现 H3K27M 神经胶质瘤主要含有类似于少突胶质细胞前体细胞（OPC 样）的细胞，而分化程度较高的恶性细胞占少数。 OPC 样细胞比分化程度更高的细胞表现出更大的增殖和肿瘤增殖潜力，并且至少部分由 PDGFRA 信号传导维持。我们的研究以单细胞分辨率和跨遗传亚克隆描述了 H3K27M 神经胶质瘤的致癌和发育程序，提出了该疾病的潜在治疗靶点。
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.
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影响因子：
64.5
作者：
Suvà ML;Rheinbay E;Gillespie SM;Patel AP;Wakimoto H;Rabkin SD;Riggi N;Chi AS;Cahill DP;Nahed BV;Curry WT;Martuza RL;Rivera MN;Rossetti N;Kasif S;Beik S;Kadri S;Tirosh I;Wortman I;Shalek AK;Rozenblatt-Rosen O;Regev A;Louis DN;Bernstein BE
通讯作者：
Bernstein BE
影响因子：
64.8
作者：
Tirosh I;Venteicher AS;Hebert C;Escalante LE;Patel AP;Yizhak K;Fisher JM;Rodman C;Mount C;Filbin MG;Neftel C;Desai N;Nyman J;Izar B;Luo CC;Francis JM;Patel AA;Onozato ML;Riggi N;Livak KJ;Gennert D;Satija R;Nahed BV;Curry WT;Martuza RL;Mylvaganam R;Iafrate AJ;Frosch MP;Golub TR;Rivera MN;Getz G;Rozenblatt-Rosen O;Cahill DP;Monje M;Bernstein BE;Louis DN;Regev A;Suvà ML
通讯作者：
Suvà ML
影响因子：
23.9
作者：
Liau BB;Sievers C;Donohue LK;Gillespie SM;Flavahan WA;Miller TE;Venteicher AS;Hebert CH;Carey CD;Rodig SJ;Shareef SJ;Najm FJ;van Galen P;Wakimoto H;Cahill DP;Rich JN;Aster JC;Suvà ML;Patel AP;Bernstein BE
通讯作者：
Bernstein BE
影响因子：
8.8
作者：
Darmanis, Spyros;Sloan, Steven A.;Quake, Stephen R.
通讯作者：
Quake, Stephen R.
影响因子：
82.9
作者：
Kreso, Antonija;van Galen, Peter;O'Brien, Catherine A.
通讯作者：
O'Brien, Catherine A.