室下区
生物
间充质干细胞
神经干细胞
祖细胞
癌症研究
免疫系统
癌症干细胞
肿瘤微环境
癌症
癌细胞
干细胞
免疫学
细胞生物学
遗传学
作者
Charles Couturier,Javad Nadaf,Zhaorong Li,Salma Baig,Gabriele Riva,Phuong Uyen Le,Daan J. Kloosterman,Jean Monlong,Andriniaina Nkili Meyong,Redouane Allache,Theresa Degenhard,Mariam Al-Rashid,Marie‐Christine Guiot,Guillaume Bourque,Jiannis Ragoussis,Leila Akkari,Francisco J. Quintana,Kevin Petrecca
出处
期刊:Neuro-oncology
[Oxford University Press]
日期:2022-04-13
卷期号:24 (9): 1494-1508
被引量:11
标识
DOI:10.1093/neuonc/noac085
摘要
Glioblastoma is a treatment-resistant brain cancer. Its hierarchical cellular nature and its tumor microenvironment (TME) before, during, and after treatments remain unresolved.Here, we used single-cell RNA sequencing to analyze new and recurrent glioblastoma and the nearby subventricular zone (SVZ).We found 4 glioblastoma neural lineages are present in new and recurrent glioblastoma with an enrichment of the cancer mesenchymal lineage, immune cells, and reactive astrocytes in early recurrences. Cancer lineages were hierarchically organized around cycling oligodendrocytic and astrocytic progenitors that are transcriptomically similar but distinct to SVZ neural stem cells (NSCs). Furthermore, NSCs from the SVZ of patients with glioblastoma harbored glioblastoma chromosomal anomalies. Lastly, mesenchymal cancer cells and TME reactive astrocytes shared similar gene signatures which were induced by radiotherapy in a myeloid-dependent fashion in vivo.These data reveal the dynamic, immune-dependent nature of glioblastoma's response to treatments and identify distant NSCs as likely cells of origin.
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