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.
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Achaete scute homolog 1
Alpha-thalassemia/mental retardation syndrome X-linked
Basic fibroblast growth factor
bone morphogenetic protein receptor 1 B
Ciliary neurotrophic factor
Embryonic stem cell
Enhancer of zeste homolog 2
Substitution of glycine 34 with arginine or valine
CpG island methylator phenotype of glioma
Glioblastoma stem cell
Histone 3, lysine 9
Hox transcript antisense intergenic RNA
Isocitrate dehydrogenase 1
Induced pluripotent stem cell
- K27 M:
Substitution of lysine 27 with methionine
Lymphoid enhancer factor
Long non-coding RNA
Notch intracellular domain
Neural stem cell
Polycomb repressor complex 1/2
Repressor element 1 silencing transcription factor
Receptor tyrosine kinase
Small C-terminal domain phosphatase 1
Signal Transducer and Activator of Transcription
The Cancer Genome Atlas
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We apologize to colleagues whose work we may not have been able to be included in this review due to space constraints.We thank all of the members of the Laboratory of Molecular Neuroscience, Department of Stem Cell Biology and Medicine, Kyushu University, for their valuable comments, and Elizabeth Nakajima for critical reading of this manuscript. This work was supported by MEXT KAKENHI (16H06527) to K. N.
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Kawamura, Y., Takouda, J., Yoshimoto, K. et al. New aspects of glioblastoma multiforme revealed by similarities between neural and glioblastoma stem cells. Cell Biol Toxicol 34, 425–440 (2018). https://doi.org/10.1007/s10565-017-9420-y
- Differentiation therapy
- Glioblastoma multiforme
- Glioblastoma stem cells
- Neural stem cells