Characterization of adult central nervous system (CNS) germinal regions, such as the subventricular zone (SVZ) and dentate gyrus, has accelerated our understanding of stem and progenitor cell populations in the postnatal vertebrate brain. Studies of these same regions in the human brain, however, have revealed surprising differences from rodents in their structure and function in rodents. Specifically, the human SVZ is robustly proliferative during infancy. Then suddenly in childhood it stops expanding. During this window of neurogenesis, however, an unprecedented migratory stream delivers SVZ neuronal progeny to the human prefrontal cortex—a phenomenon without parallel in any other studied vertebrate, including primates.
These findings underline the significance of studying progenitor populations in the human brain. Importantly, recent work suggests that gliomas, the most common primary brain tumor in humans, are initiated by glioma stem cells derived from postnatal glial progenitor cells (GPCs)—lineage-restricted cells that produce oligodendrocytes and astrocytes.
Interestingly, GPCs are the most abundant progenitor cell population in the adult mammalian brain. Yet, the organization and composition of their niche in the subcortical white matter remains unexplored. Our laboratory’s efforts are aimed at characterizing human GPCs and their germinal niche, and at developing a new set of human GPC-specific transcriptional and metabolic markers that enable real-time tracking of GPCs and glioma stem cells in live human brain. Additional work is being pursued to improve the characterization of the role of cell polarity in progenitor and glioma-derived progenitor cells.