Characterization of Adult Neural Stem Cells and Their Relation to Brain Tumors

Abstract

The adult mammalian brain contains neural stem cells that are capable of generating new neurons and glia over the course of a lifetime. Neural stem cells reside in 2 germinal niches, the subventricular zone (SVZ) and the dentate gyrus subgranular zone. These primary progenitors have been identified in their niche in vivo; these cells have characteristics of astrocytes. Recent studies have shown that adult SVZ stem cells are derived from radial glia, the stem cells in the developing brain, which in turn are derived from the neuroepithelum, the earliest brain progenitors. Thus, SVZ stem cells are a continuum from neuroepithelium to radial glia to astrocytes, and are contained within what has been considered the lineage for astrocytes. However, it seems that only a small subset of the astrocytes present in the adult brain have stem cell properties. Recent findings have shown that SVZ stem cell astrocytes express a receptor for platelet-derived growth factor (PDGF), suggesting that the ability to respond to specific growth factor stimuli, such as PDGF, epidermal growth factor and others, may be unique to these stem cell astrocytes. Intriguingly, activation of these same signaling pathways is widely implicated in brain tumor formation. Since the adult brain has very few proliferating cells capable of accumulating the numerous mutations required for transformation, the adult neural stem and/or progenitor cells may be likely candidates for the brain tumor cell of origin. Indeed, activation of the PDGF or epidermal growth factor pathways in adult neural stem or progenitor cells confers tumor-like properties on these cells, lending support to this hypothesis.

Transition toward Human Cytomegalovirus Susceptibility in Early Human Embryonic Stem Cell-Derived Neural Precursors

“…1D). Our findings trace the switch toward HCMV susceptibility to early neural precursors, representing the primitive neuroepithelial cells (24,25,28), which form the neural plate and neural tube as early as 4 weeks of gestation-later giving rise to the progenitors of neural stem cells (28)(29)(30)(31)(32). Viral targeting of these primary predecessors of the developing nervous system could underlie the progressive neurodevelopmental disabilities associated with congenital HCMV infection.…”

“…The mechanism by which PDGFR␣ regulates HCMV infection in hESC-derived NPC remains to be determined. In view of the documented functions of PDGFR␣ during neurodevelopment (30,(40)(41)(42)(43)(44)(45)(46)(47), it is tempting to speculate that its engagement by HCMV and its virus-induced downregulation (48) could be a key factor in the neuropathogenesis of congenital HCMV. Our findings do not exclude a role for other potential cofactors (including additional surface receptors) in modulating the increased viral susceptibility during differentiation, which could be further analyzed by global gene expression studies.…”

The role of cancer stem cells in glioblastoma

“…The hierarchy is dynamic with respect to cell type (CSCs, non-CSCs) and is maintained by the balance between self-renewal and differentiation. 43,107 Viewed in this light, tumors can be thought of as aberrant organs comprising heterogeneous cell types derived from CSCs rather than simply an accumulation of diverse neoplastic clones.…”

“…43,113 There are many common pathways between CSCs and NSCs that are involved in neural development, including Notch, Wnt, and transforming growth factor-b (TGF-b) signaling. 32,89 Oligodendrogenesis relies on platelet-derived growth factor (PDGF); increased PDGF signaling has been demonstrated to cause abnormal NSC proliferation and glioma formation.…”

“…The hierarchy is dynamic with respect to cell type (CSCs, non-CSCs) and is maintained by the balance between self-renewal and differentiation. 43,107 Viewed in this light, tumors can be thought of as aberrant organs comprising heterogeneous cell types derived from CSCs rather than simply an accumulation of diverse neoplastic clones.Researchers who made the initial attempts to define CSCs described a qualitatively distinct population of pathological cells that was able to self-renew and ir- Recurrence in glioblastoma is nearly universal, and its prognosis remains dismal despite significant advances in treatment over the past decade. Glioblastoma demonstrates considerable intratumoral phenotypic and molecular heterogeneity and contains a population of cancer stem cells that contributes to tumor propagation, maintenance, and treatment resistance.…”