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对II型神经母细胞极性破坏引发的脑癌进行全转录组分析。

Transcriptome-Wide Analysis of Brain Cancer Initiated by Polarity Disruption in Type II Neuroblasts.

作者信息

Paglia Simona, Morciano Patrizia, de Biase Dario, Giorgi Federico Manuel, Pession Annalisa, Grifoni Daniela

机构信息

Department of "Pharmacy and Biotechnology", University of Bologna, Via Selmi 3, 40126 Bologna, Italy.

Department of "Life Health and Environmental Sciences", University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.

出版信息

Int J Mol Sci. 2025 May 26;26(11):5115. doi: 10.3390/ijms26115115.

Abstract

Brain tumors, in particular gliomas and glioblastoma multiforme (GBM), are thought to originate from different cells facing specific founding insults, a feature that partly justifies the complexity and heterogeneity of these severe forms of cancer. However, gliomas and GBM are usually reproduced in animal models by inducing molecular alterations in mature glial cells, which, though being part of the puzzle, do not represent the whole picture. To fill this conceptual gap, we previously developed a neurogenic model of brain cancer in , demonstrating that the loss of cell polarity in neural stem cells (called neuroblasts in the fruit fly) is sufficient to promote the formation of malignant masses that continue to grow in the adult, displaying several phenotypic traits typical of human GBM. Here, we expand on previous work by restricting polarity disruption to type II neuroblasts, whose self-renewal is comparable to that of mammalian neural progenitors, with the aim to capture the molecular signature of the resulting cancers in a specific and reproducible context. A comparison of the most deregulated transcripts with those found in human primary GBMs confirmed that our model can be proficiently used to delve into the roots of human brain tumorigenesis.

摘要

脑肿瘤,尤其是胶质瘤和多形性胶质母细胞瘤(GBM),被认为起源于面临特定起始损伤的不同细胞,这一特征在一定程度上解释了这些严重癌症形式的复杂性和异质性。然而,胶质瘤和GBM通常是通过在成熟神经胶质细胞中诱导分子改变在动物模型中重现的,这些成熟神经胶质细胞虽然是其中一部分,但并不代表全貌。为了填补这一概念空白,我们之前在[具体实验对象]中建立了一种脑癌神经发生模型,证明神经干细胞(果蝇中称为神经母细胞)中细胞极性的丧失足以促进恶性肿块的形成,这些肿块在成体中持续生长,表现出人类GBM的几种典型表型特征。在这里,我们通过将极性破坏限制在II型神经母细胞上来扩展之前的工作,II型神经母细胞的自我更新与哺乳动物神经祖细胞相当,目的是在一个特定且可重复的背景下捕捉由此产生的癌症的分子特征。将最失调的转录本与人类原发性GBM中发现的转录本进行比较,证实我们的模型可有效地用于深入探究人类脑肿瘤发生的根源。

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