Mapping chromatin remodelling in glioblastoma identifies epigenetic regulation of key molecular pathways and novel druggable targets.

IF 4.5 1区 生物学 Q1 BIOLOGY BMC Biology Pub Date : 2025-02-07 DOI:10.1186/s12915-025-02127-9
Claire Vinel, James Boot, Weiwei Jin, Nicola Pomella, Alexandra Hadaway, Charles Mein, Nicolae Radu Zabet, Silvia Marino
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Abstract

Background: Glioblastoma is the most common and aggressive malignant brain tumour in the adult population and its prognosis is dismal. The heterogeneous nature of the tumour, to which epigenetic dysregulation significantly contributes, is among the main therapeutic challenges of the disease.

Results: We have leveraged SYNGN, an experimental pipeline enabling the syngeneic comparison of glioblastoma stem cells and expanded potential stem cell (EPSC)-derived neural stem cells to identify regulatory features driven by chromatin remodelling specifically in glioblastoma stem cells.

Conclusions: We show epigenetic regulation of the expression of genes and related signalling pathways contributing to glioblastoma development. We also identify novel epigenetically regulated druggable target genes on a patient-specific level, including SMOX and GABBR2.

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在胶质母细胞瘤中绘制染色质重塑图谱,确定关键分子途径的表观遗传调控和新的药物靶点。
背景:胶质母细胞瘤是成人中最常见、侵袭性最强的恶性脑肿瘤,其预后较差。肿瘤的异质性,其中表观遗传失调显著贡献,是该疾病的主要治疗挑战之一。结果:我们利用SYNGN,一个实验管道,能够进行胶质母细胞瘤干细胞和扩增潜能干细胞(EPSC)衍生的神经干细胞的同质性比较,以确定胶质母细胞瘤干细胞中染色质重塑驱动的调节特征。结论:我们发现基因表达的表观遗传调控和相关的信号通路有助于胶质母细胞瘤的发展。我们还在患者特异性水平上发现了新的表观遗传调控的可药物靶基因,包括SMOX和GABBR2。
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来源期刊
BMC Biology
BMC Biology 生物-生物学
CiteScore
7.80
自引率
1.90%
发文量
260
审稿时长
3 months
期刊介绍: BMC Biology is a broad scope journal covering all areas of biology. Our content includes research articles, new methods and tools. BMC Biology also publishes reviews, Q&A, and commentaries.
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