Stem-04. Unveiling Glioblastoma Origin-cells: Isolation and Characterization From the Subventricular Zone
Year: 2024
Type: conference-abstract
Abstract: Glioblastoma (GBM) may originate from somatic mutations within the subventricular zone (SVZ). We investigated putative GBM origin-cells in the SVZ with somatic mutations implicated in GBM development. We hypothesized these origin-cells have unique properties compared to tumor-derived GBM tumorspheres (TSs). We isolated, characterized, and analyzed mouse transcriptomes of GBM origin-cells and GBM TSs, and sought to identify potential human GBM origin-cells within the SVZ. Using a mouse model with somatic mutations (Trp53/Pten/hEGFRvIII) induced within the SVZ, we demonstrated that mutated cells in the SVZ migrate to the cortex and form GBM. We isolated mouse GBM (mGBM) origin-cells from the SVZ and mGBM TSs from the tumors, comparing their characteristics, transcriptome, and tumorigenic potential upon orthotopic or SVZ injection. To identify potential human GBM origin-cells, single-nucleus RNA sequencing (snRNAseq) was performed on human GBM SVZ specimens. Our investigation revealed intriguing properties and distinct gene expression patterns in GBM origin-cells. mGBM origin-cells from the SVZ somatic mutation model demonstrated enhanced stemness and invasiveness compared to control SVZ cells. These cells exhibited site-specific tumorigenic capacity: cortical injection of mGBM origin-cells failed to induce tumor formation, while re-injection into the SVZ led to migration to the cortex and tumor development. RNA sequencing revealed significant gene expression differences between mGBM origin-cells and mGBM TSs despite similar mutation profiles, suggesting distinct identities. snRNAseq analysis of human GBM SVZ specimens (pathologically tumor-free) identified cells with chromosomal aberrations characteristic of early GBM development, including chromosome 7 gain / 10 loss. These findings suggest potential human GBM origin-cells within the SVZ. This study describes a distinct population of GBM origin-cells within the SVZ, different from tumor-derived cancer stem cells. These GBM origin-cells exhibit unique properties, including enhanced stemness and invasiveness, and display site-specific tumorigenic capacity, forming tumors only in the SVZ environment. Further research into the factors that cause GBM origin-cells in the SVZ to migrate and form tumors in the cortex is crucial.
Source: Neuro-Oncology
Institutions: Yonsei University, Severance Hospital, Yonsei University Health System, Sungkyunkwan University, Korea Advanced Institute of Science and Technology, Korea University, Korea University Medical Center, Seoul National University, Seoul National University Hospital, Gangnam Severance Hospital
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4404256906