PDGF-Responsive Progenitors Persist in the Subventricular Zone across the Lifespan

Abstract

The SVZ (subventricular zone) contains neural stem cells and progenitors of various potentialities. Although initially parsed into A, B, and C cells, this germinal zone is comprised of a significantly more diverse population of cells. Here, we characterized a subset of postnatal PRPs (PDGF-AA-responsive precursors) that express functional PDGFα and β receptors from birth to adulthood. When grown in PDGF-AA, dissociated neonatal rat SVZ cells divided to produce non-adherent clusters of progeny. Unlike the self-renewing EGF/FGF-2-responsive precursors that produce neurospheres, these PRPs failed to self-renew after three passages; therefore, we refer to the colonies they produce as spheroids. Upon differentiation these spheroids could produce neurons, type 1 astrocytes and oligodendrocytes. When maintained in medium supplemented with BMP-4 they also produced type 2 astrocytes. Using lineage tracing methods, it became evident that there were multiple types of PRPs, including a subset that could produce neurons, oligodendrocytes, and type 1 and type 2 astrocytes; thus some of these PRPs represent a unique population of precursors that are quatropotential. Spheroids also could be generated from the newborn neocortex and they had the same potentiality as those from the SVZ. By contrast, the adult neocortex produced less than 20% of the numbers of spheroids than the adult SVZ and spheroids from the adult neocortex only differentiated into glial cells. Interestingly, SVZ spheroid producing capacity diminished only slightly from birth to adulthood. Altogether these data demonstrate that there are PRPs that persist in the SVZ that includes a unique population of quatropotential PRPs.

Resolving the transcriptional transitions associated with oligodendrocyte generation from adult neural stem cells by single cell sequencing

“…derived from this analysis include "Circadian clock", which has not previously been described as a regulator of oligodendrogenesis, although an earlier study proposed this pathway as a cell-intrinsic timer for inhibiting cell division in postnatal OPCs (Gao, Durand, & Raff, 1997). Interestingly, PDGF signaling was uniquely enriched in OLpNSCs in our analysis and we predict that this oligodendrocyte lineage stage comprises the SVZ cell population previously reported to undergo in vivo expansion upon exposure to infused PDGF-A (Jackson et al, 2006;Moore, Bain, Loh, & Levison, 2014). Pathways detected in aNSC and TAP populations comprise "Cell cycle", "DNA/nucleotide synthesis" and "Transcriptional machineries", consistent with single cell profiling studies of adult neurogenesis (Dulken et al, 2019;Llorens-Bobadilla et al, 2015).…”

Connections between Early-Life Neuroinflammation, Neural Stem Cells and Progenitors and Origins of Neuropsychiatric Disorders

“…These were the CD133+LeX+NG2-CD140a-(NSC), CD133-LeX+NG2-CD140a-(MP1), CD133+LeX+NG2+ CD140a-(MP2), CD133+LeX+NG2+CD140a+ (MP4) and CD133-LeX+NG2+CD140a+ (referred to as PDGFR -FGF2-responsive MPs: PFMP). This PFMP is likely the NG2+ multipotential progenitor that has been isolated from the embryonic forebrain [54] and is similar to the PDGF responsive progenitors present in the neonatal rat SVZ as described by Moore et al, 2014 [57].…”

Hyperoxia Inhibits the Growth of Mouse Forebrain Oligodendrocyte Progenitors

“…Another major difference in our method for culturing mouse OPCs was to decrease their exposure to oxygen. Our previous studies have shown that neural progenitor cell proliferation and differentiation can be affected by growth in 20% vs. 2% oxygen incubators [52]. Yet other studies have shown that oxygen tension is a critical determinant in NSC propagation whereas growth in 5% O 2 expanded Nestin+/CD133+/CD24+ precursors that readily differentiated into all three neural lineages [38,39].…”