PDGFR  Expression Distinguishes GFAP-Expressing Neural Stem Cells from PDGF-Responsive Neural Precursors in the Adult Periventricular Area

Abstract

Jackson et al. (2006) have reported that adult glial fibrillary acid protein (GFAP)-expressing neural stem cells (NSCs) also express platelet-derived growth factor (PDGF) receptor-␣ (PDGFR␣), and that their stimulation by PDGF induced the formation of a glioma-like mass. Here, we reexamined the relationship between PDGFR␣ and GFAP expression within the three-dimensional organization of the adult periventricular area. Using four independent PDGFR␣ antibodies, we found that adult mouse GFAP-expressing NSCs and PDGFR␣-expressing cells represent two distinct populations of neural precursors. Examination of the adult periventricular area in a mouse line that expresses nuclear-localized enhanced green fluorescent protein under the control of the PDGFR␣ promoter confirmed that GFAP-expressing NSCs do not express PDGFR␣. Furthermore, PDGF-responsive neural precursors were found at least one cell layer subjacent to the ependymal layer, and were evenly distributed across the lateral ventricular wall, which contrasts with the reported patchy and often ependymal localization of adult GFAP-expressing NSCs. Adult human PDGFR␣-expressing neural precursors were also found not to express GFAP. PDGF-responsive neural precursors, but not GFAP-expressing NSCs, responded to infusions of PDGF by generating glioma-like masses. Our results do not support the view that GFAP-expressing NSCs are the origin of glioma-like masses that form after intraventricular PDGF infusion.

PEDF Is a Novel Oligodendrogenic Morphogen Acting on the Adult SVZ and Corpus Callosum

“…It has previously been reported that a subset of GFAP+ cells in adult mouse SVZ expresses PDGFrα (Jackson et al, 2006), suggesting the presence of SVZ GFAP+ neural precursor cells with early specification towards the oligodendroglial lineage. In contrast, Chojnacki et al (2011) reported the absence of GFAP and PDGFrα double-positive cells in the adult mouse SVZ. Employing GFAP:GFP transgenic mice allowed us to visualize GFAP+ cells and to firmly discriminate between GFAP+ and PDGFrα+ cells in the SVZ.…”

The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis

“…Platelet-derived growth factor (PDGF) signaling appears to play a role in balancing neuronal and oligodendrocyte production from the V-SVZ, and excessive PDGF signaling from ventricular infusion results in hyperplasia with some features of gliomas. Initial findings suggested that a significant subpopulation of cells within the hyperplasias is derived from type B1 cells (Jackson et al 2006); however, more recent work suggests that the majority, if not all, PDGF-responsive cells are oligodendroglial progenitors within the V-SVZ (Chojnacki et al 2011). Vascular endothelial growth factor (VEGF), a known angiogenic protein, also stimulates V-SVZ neurogenesis when infused into the ventricle (Jin et al 2002b), suggesting a link between angiogenesis and neurogenesis (Palmer et al 2000;Louissaint et al 2002;Greenberg and Jin 2005).…”

Intraspinal Transplantation of Mouse and Human Neural Precursor Cells

“…Additionally, the cells should be OCT4 (POU5F1) negative; OCT4 is a pluripotency marker expressed on ESCs (Boiani and Scholer, 2005). NPCs should also be negative for GFAP (astrocytes), PDGFRalpha (oligodendrocytes) and MAP2 (neurons), as this would indicate further differentiation and loss of multipotency (Chojnacki et al, 2011; Jacque et al, 1978; Shafit-Zagardo and Kalcheva, 1998). …”