Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states.
Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states.
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重新卷积原发性和复发性胶质母细胞瘤的组成景观揭示了预后和靶向组织状态。
DOI：
10.1038/s41467-023-38186-1
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发表时间：
2023-05-04
影响因子：
16.6
通讯作者：
Canoll, Peter
中科院分区：
文献类型：
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作者：
Al-Dalahmah, Osama;Argenziano, Michael G. G.;Kannan, Adithya;Mahajan, Aayushi;Furnari, Julia;Paryani, Fahad;Boyett, Deborah;Save, Akshay;Humala, Nelson;Khan, Fatima;Li, Juncheng;Lu, Hong;Sun, Yu;Tuddenham, John F. F.;Goldberg, Alexander R. R.;Dovas, Athanassios;Banu, Matei A. A.;Sudhakar, Tejaswi;Bush, Erin;Lassman, Andrew B. B.;McKhann, Guy M. M.;Gill, Brian J. A.;Youngerman, Brett;Sisti, Michael B. B.;Bruce, Jeffrey N. N.;Sims, Peter A. A.;Menon, Vilas;Canoll, Peter
胶质母细胞瘤（GBM）弥漫性浸润脑并与非肿瘤性脑细胞（包括星形胶质细胞、神经元和小胶质细胞/骨髓细胞）混合。这种细胞类型的复杂混合物形成了治疗反应和肿瘤复发的生物学背景。我们使用单核RNA测序和空间转录组学来确定原发性和复发性胶质瘤的细胞组成和转录状态，并确定了由肿瘤性和非肿瘤性脑细胞的特定亚群之间的同居模式定义的三种组成性“组织状态”。这些组织状态与影像学、组织病理学和预后特征相关，并在不同的代谢途径中富集。脂肪酸生物合成在由星形胶质细胞样/间充质胶质瘤细胞、反应性星形胶质细胞和巨噬细胞的同居所定义的组织状态中富集，并且与复发性GBM和较短的生存期相关。用脂肪酸合成抑制剂治疗急性GBM切片，可以消除这种有害组织状态的转录特征。这些发现指向靶向GBM微环境中的相互依赖性的疗法。胶质母细胞瘤（GBM）细胞可以浸润到肿瘤微环境（TME）中并导致复发。在这里，作者使用单核和空间转录组学分析了原发性和复发性GBM及其TME，揭示了由肿瘤和非肿瘤细胞组合定义的组织状态，这可能是治疗靶点。
Glioblastoma (GBM) diffusely infiltrates the brain and intermingles with non-neoplastic brain cells, including astrocytes, neurons and microglia/myeloid cells. This complex mixture of cell types forms the biological context for therapeutic response and tumor recurrence. We used single-nucleus RNA sequencing and spatial transcriptomics to determine the cellular composition and transcriptional states in primary and recurrent glioma and identified three compositional ‘tissue-states’ defined by cohabitation patterns between specific subpopulations of neoplastic and non-neoplastic brain cells. These tissue-states correlated with radiographic, histopathologic, and prognostic features and were enriched in distinct metabolic pathways. Fatty acid biosynthesis was enriched in the tissue-state defined by the cohabitation of astrocyte-like/mesenchymal glioma cells, reactive astrocytes, and macrophages, and was associated with recurrent GBM and shorter survival. Treating acute slices of GBM with a fatty acid synthesis inhibitor depleted the transcriptional signature of this pernicious tissue-state. These findings point to therapies that target interdependencies in the GBM microenvironment. Glioblastoma (GBM) cells can infiltrate into the tumour microenvironment (TME) and contribute to recurrence. Here, the authors analyse primary and recurrent GBMs and their TME using single-nucleus and spatial transcriptomics, revealing tissue states defined by the combinations of neoplastic and non-neoplastic cells, which could be therapeutic targets.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
14.8
作者：
Krishnaswami SR;Grindberg RV;Novotny M;Venepally P;Lacar B;Bhutani K;Linker SB;Pham S;Erwin JA;Miller JA;Hodge R;McCarthy JK;Kelder M;McCorrison J;Aevermann BD;Fuertes FD;Scheuermann RH;Lee J;Lein ES;Schork N;McConnell MJ;Gage FH;Lasken RS
通讯作者：
Lasken RS
影响因子：
18.4
作者：
Levitin HM;Yuan J;Sims PA
通讯作者：
Sims PA
影响因子：
3.9
作者：
Grube, Susanne;Duenisch, Pedro;Ewald, Christian
通讯作者：
Ewald, Christian