An Exploratory Computational Study on the Putative Links Between Neurogenesis and Glioblastoma Development: Post-Ischemic Macaque Subventricular Zone and Human Glioblastoma Show Limited Transcriptomic Concordance

Background/Objectives: Glioblastoma (GBM) is the most malignant primary brain tumor in humans, and it is characterized by frequent relapses and poor prognosis. GBMs contain self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumor initiation and therapeutic resistance. It has been proposed that GBM CSCs originate from neural stem cells (NSCs) residing in the adult subventricular zone (SVZ), enclosing the driver mutations of human GBM. We have previously established a model of transient global ischemia in adult macaque monkeys, where we found that SVZ shows a transcriptional profile reminiscent of a profile typical for quiescent NSCs, uncovering novel gene markers for SVZ, such as the apelin receptor (APLNR). Methods: Here we conducted a deep whole genome transcriptomics analysis to compare the gene expression changes of the macaque monkey SVZ occurring in response to transient global cerebral ischemia with those involved in human SVZ neurogenesis (NSCs) or in GBM. Results/Conclusions: Overlap was narrow: only 15 genes were deregulated in all three datasets, and eight of them (including NES, GFAP and CHI3L1) were upregulated both after ischemia and in GBM. Shared pathway signals (Wnt, ERBB4) nominate testable candidates, but the datasets diverge globally and do not by themselves establish the ischemic macaque SVZ as a discovery platform for human GBM.