小胶质细胞
表型
胶质瘤
瞬态(计算机编程)
DNA甲基化
癌症研究
甲基化
还原(数学)
DNA
化学
生物
基因
免疫学
炎症
计算机科学
基因表达
生物化学
操作系统
数学
几何学
作者
Mathilde Cheray,Adriana‐Natalia Murgoci,Adamantia F. Fragopoulou,Carlos Rodrigues,Martin Skandik,A. Osman,Christine Hong,Guillermo Vázquez-Cabrera,Lara Frieß,Lena-Maria Carlson,Shigeaki Kanatani,Yue Li,Anastasios Damdimopoulos,Per Uhlén,Fredrik Kamme,Klas Blomgren,Bertrand Joseph
出处
期刊:
[Cold Spring Harbor Laboratory]
日期:2025-02-27
标识
DOI:10.1101/2025.02.22.639606
摘要
Abstract Glioblastoma, aggressive primary brain tumors with a dismal prognosis, promote the recruitment of microglia, brain resident innate immune cells, and ultimately their activation toward a tumor-supportive phenotype that increases gliomal proliferation and invasion capability. Here, we report that upon stimulation by glioma cells, microglia transit via a reactive state holding anti-tumoral properties coupled to reduced DNMT3A chromatin occupancy and DNA demethylation that promote microglial pro-inflammatory gene expressions. We find that upon repression of Dnmt3a expression in microglia, those cells maintain anti-tumoral attributes in vitro and in vivo . In a syngeneic immunocompetent glioblastoma mouse model, brain delivery of antisense oligonucleotide targeting Dnmt3a expression led to reduced tumor growth. Taken together, our results reveal the involvement of DNA demethylation in the control of glioma cells-induced microglia activation and indicate that microglial DNMT3A is a potentially therapeutic target to treat brain neoplasms such as glioblastoma that include a microglial component.
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