Allache, R. | Search bioRxiv

bioRxiv2023

Identity and Nature of Neural Stem Cells in the Adult Human Subventricular Zone

The existence of neural stem cells (NSCs) in adult human brain neurogenic regions remains unresolved. To address this, we created a cell atlas of the adult human subventricular zone (SVZ) derived from fresh neurosurgical samples using single-cell transcriptomics. We discovered 2 adult radial glia (RG)-like populations, aRG1 and aRG2. aRG1 shared features with fetal early RG (eRG) and aRG2 were transcriptomically similar to fetal outer RG (oRG). We also captured early neuronal and oligodendrocytic NSC states. We found that the biological programs driven by their transcriptomes support their roles as early-lineage NSCs. Finally, we show that these NSCs have the potential to transition between states and along lineage trajectories. These data reveal that multipotent NSCs reside in the adult human SVZ.

neuroscience↗

bioRxiv2018

Single-cell RNA-seq reveals that glioblastoma recapitulates normal brain development

SummaryCancer stem cells are critical for cancer initiation, development, and resistance to treatments. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To overcome these limitations, we performed single-cell RNA-sequencing on 38 296 glioblastoma cells and 22 637 normal human fetal brain cells. Using an unbiased approach, we mapped the lineage hierarchy of the developing human brain and compared the transcriptome of each cancer cell to this roadmap. We discovered a conserved neural trilineage cancer hierarchy with glial progenitor-like cells at the apex. We also found that this progenitor population contains the majority of cancers cycling cells and is the origin of heterogeneity. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, unravels the origin of glioblastoma heterogeneity, and helps to identify cancer stem cell-specific targets.

cancer biology↗