Article

Jackson, E.L. et al. PDGFR-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 51, 187-199

Department of Neurological Surgery and Program in Developmental and Stem Cell Biology, University of California, San Francisco, San Francisco, California 94143, USA.
Neuron (Impact Factor: 15.05). 08/2006; 51(2):187-99. DOI: 10.1016/j.neuron.2006.06.012
Source: PubMed

ABSTRACT

Neurons and oligodendrocytes are produced in the adult brain subventricular zone (SVZ) from neural stem cells (B cells), which express GFAP and have morphological properties of astrocytes. We report here on the identification B cells expressing the PDGFRalpha in the adult SVZ. Specifically labeled PDGFRalpha expressing B cells in vivo generate neurons and oligodendrocytes. Conditional ablation of PDGFRalpha in a subpopulation of postnatal stem cells showed that this receptor is required for oligodendrogenesis, but not neurogenesis. Infusion of PDGF alone was sufficient to arrest neuroblast production and induce SVZ B cell proliferation contributing to the generation of large hyperplasias with some features of gliomas. The work demonstrates that PDGFRalpha signaling occurs early in the adult stem cell lineage and may help regulate the balance between oligodendrocyte and neuron production. Excessive PDGF activation in the SVZ in stem cells is sufficient to induce hallmarks associated with early stages of tumor formation.

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    • "Adult neurogenesis is a multistep process in which neural stem cell (NSC) lineages progress through a series of well characterized cell stages to generate functional interneurons in the olfactory bulb and hippocampal dentate gyrus (Ming and Song, 2011; Lim and Alvarez-Buylla, 2014). In the subventricular zone (SVZ), quiescent radial glial-like (RGL) progenitor cells are the multi-potent NSC population (Doetsch et al., 1999) and are capable of undergoing symmetrical cell division to maintain the stem cell pool and asymmetric cell division to generate rapidly dividing transit amplifying cells (also referred to as intermediate progenitors), as well as astrocytes and oligodendrocytes (Doetsch et al., 1997; Jackson et al., 2006; Bonaguidi et al., 2011). Transit amplifying cells differentiate into neuroblasts that migrate to the olfactory bulb through the rostral migratory stream (RMS) to settle as interneurons in the periglomerular and granule cell layers (Lois et al., 1996; Alvarez-Buylla and Garcia-Verdugo, 2002; Ming and Song, 2011). "
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    • "Mutations activating receptor tyrosine kinase-PI3K-mTOR signaling, including platelet-derived growth factor (PDGF) receptors , are common in low-grade gliomas, and increased PDGF signaling induces glioma-like growths from the subventricular zone (SVZ) in mice (Jackson et al., 2006; Suzuki et al., 2015). We addressed whether Notch signaling cells contribute to growth factor-induced hyperplasias in the brain and infused PDGF into the lateral ventricle of adult Hes5::GFP Notch-reporter mice (Figures 1A–1E). "
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    • "It is possible that a common cell of origin, such as the previously proposed neural stem cell (Galli et al., 2004), exists for all GBMs and that the classes presented here result from distinct differentiation paths. However, the presence of precursor cells with selfreplicating ability in the brain, such as cells expressing stem cell markers and PDGFRA or EGFR (Jackson et al., 2006), suggests that multiple stem cell-like populations exist. Although there is a clear need for conclusive evidence supporting this hypothesis, it is at least striking to find the same genes as markers of two of the four classes lending support for a difference in cell of origin. "
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