Division of Basic Stem Cell Biology, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cell Biol Toxicol. 2018 Dec;34(6):425-440. doi: 10.1007/s10565-017-9420-y. Epub 2018 Jan 31.
Neural stem cells (NSCs) undergo self-renewal and generate neurons and glial cells under the influence of specific signals from surrounding environments. Glioblastoma multiforme (GBM) is a highly lethal brain tumor arising from NSCs or glial precursor cells owing to dysregulation of transcriptional and epigenetic networks that control self-renewal and differentiation of NSCs. Highly tumorigenic glioblastoma stem cells (GSCs) constitute a small subpopulation of GBM cells, which share several characteristic similarities with NSCs. GSCs exist atop a stem cell hierarchy and generate heterogeneous populations that participate in tumor propagation, drug resistance, and relapse. During multimodal treatment, GSCs de-differentiate and convert into cells with malignant characteristics, and thus play critical roles in tumor propagation. In contrast, differentiation therapy that induces GBM cells or GSCs to differentiate into a neuronal or glial lineage is expected to inhibit their proliferation. Since stem cell differentiation is specified by the cells' epigenetic status, understanding their stemness and the epigenomic situation in the ancestor, NSCs, is important and expected to be helpful for developing treatment modalities for GBM. Here, we review the current findings regarding the epigenetic regulatory mechanisms of NSC fate in the developing brain, as well as those of GBM and GSCs. Furthermore, considering the similarities between NSCs and GSCs, we also discuss potential new strategies for GBM treatment.
神经干细胞（NSCs）在周围环境特定信号的影响下，经历自我更新并产生神经元和神经胶质细胞。多形性胶质母细胞瘤（GBM）是一种高度致命的脑肿瘤，起源于 NSCs 或神经胶质前体细胞，由于转录和表观遗传网络的失调，这些网络控制 NSCs 的自我更新和分化。高度致瘤性胶质母细胞瘤干细胞（GSCs）构成了 GBM 细胞的一小部分亚群，它们与 NSCs 具有几个相似的特征。GSCs 存在于干细胞层次结构的顶端，产生参与肿瘤增殖、耐药和复发的异质群体。在多模态治疗过程中，GSCs 去分化并转化为具有恶性特征的细胞，因此在肿瘤增殖中发挥关键作用。相比之下，诱导 GBM 细胞或 GSCs 分化为神经元或神经胶质谱系的分化治疗有望抑制其增殖。由于干细胞的分化由细胞的表观遗传状态决定，因此了解其干性和祖细胞 NSCs 的表观基因组情况非常重要，并有望为 GBM 的治疗方法的开发提供帮助。在这里，我们回顾了有关发育中大脑 NSCs 命运的表观遗传调控机制、GBM 和 GSCs 的相关研究进展。此外，鉴于 NSCs 和 GSCs 之间的相似性，我们还讨论了治疗 GBM 的潜在新策略。
