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Uncovering glioblastoma origin cells: Isolation and characterization from the subventricular zone

ABSTRACT: Glioblastoma (GBM), which has a poor prognosis despite aggressive treatments, likely originates from specific cells that acquire somatic mutations within the subventricular zone (SVZ), distant from the primary tumor site. However, the properties of GBM origin cells (OCs) residing in the SVZ remain largely unknown. In this study, we isolated and characterized GBM-OCs from the SVZ using a mouse model. Exome analyses of the mouse models revealed significant copy number alterations as GBM-OCs progressed to tumors in the model. RNA analysis of human SVZ samples from GBM patients identified chromosomal alterations (7 gain/10 loss), similar to those observed in early human GBM development. These alterations were predominantly found in neural stem cell-like (NSC-like), astrocyte-like (AC-like), and oligodendrocyte precursor cell-like (OPC-like) populations. This study identifies GBM-OCs in the SVZ of mice and humans, highlighting their distinct features, and suggests that these cells could serve as target cells for future GBM treatments.

ORGANISM(S): Homo sapiens

PROVIDER: GSE301596 | GEO | 2026/01/01

REPOSITORIES: GEO

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Project description:Throughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to evaluate potential heterogeneity in the NSC pool, we microdissected the dorsal and lateral SVZ at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors influenced NSC specification indicating that the fate of regionalized postnatal SVZ NSCs can be readily modified . These findings reveal functional heterogeneity of NSCs in the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts. Microarrays of neural stem cells, early progenitors and the tissue from subregions of the subventricular zone were compiled to screen for the full extent of heterogeneity in this region during postnatal life. Spatially distinct regions of the developing forebrain subventricular zone (SVZ) aged at P4, P8 and P11 were microdissected in RNAse free/sterile conditions. Mice expressing Ascl1-EGFP in the SVZ were used to aid accurate microdissection of the dorsal and lateral wall of each of the studied time points as per our previous publications characterizing this method. As well as at the whole microdomain level, additionally, NSCs (Hes5-EGFP+/Prom1+) and early progenitors (Ascl1-EGFP+) from each microdomain were further isolated by FAC sorting methods. This was to provide a comprehensive gene expression analysis at the tissue level and at the cellular level. Generally, 1 litter was used to yield 1 'n' number of replicates. A total of 23 affymetrix analysis were performed.

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Uncovering glioblastoma origin cells: Isolation and characterization from the subventricular zone

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