Adult SVZ Stem Cells Lie in a Vascular Niche: A Quantitative Analysis of Niche Cell-Cell Interactions

New York Neural Stem Cell Institute, Rensselaer, NY 12144, USA.
Cell stem cell (Impact Factor: 22.27). 10/2008; 3(3):289-300. DOI: 10.1016/j.stem.2008.07.026
Source: PubMed


There is an emerging understanding of the importance of the vascular system within stem cell niches. Here, we examine whether neural stem cells (NSCs) in the adult subventricular zone (SVZ) lie close to blood vessels, using three-dimensional whole mounts, confocal microscopy, and automated computer-based image quantification. We found that the SVZ contains a rich plexus of blood vessels that snake along and within neuroblast chains. Cells expressing stem cell markers, including GFAP, and proliferation markers are closely apposed to the laminin-containing extracellular matrix (ECM) surrounding vascular endothelial cells. Apical GFAP+ cells are admixed within the ependymal layer and some span between the ventricle and blood vessels, occupying a specialized microenvironment. Adult SVZ progenitor cells express the laminin receptor alpha6beta1 integrin, and blocking this inhibits their adhesion to endothelial cells, altering their position and proliferation in vivo, indicating that it plays a functional role in binding SVZ stem cells within the vascular niche.

Full-text preview

Available from:
  • Source
    • "Neural stem cells (NSCs) are residing in niches along the ventricular neuraxis of the mammalian nervous system (Craig et al. 1996; Golmohammadi et al. 2008; Mirzadeh et al. 2008; Shen et al. 2008). They are capable of selfrenewal , prolonged cell division, and generating a large number of progeny (Reynolds and Weiss 1992). "
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionNeural stem cells (NSCs) reside along the ventricular axis of the mammalian brain. They divide infrequently to maintain themselves and the down-stream progenitors. Due to the quiescent property of NSCs, attempts to deplete these cells using antimitotic agents such as cytosine b-Aarabinofuranoside (Ara-C) have not been successful. We hypothesized that implementing infusion gaps in Ara-C kill paradigms would recruit the quiescent NSCs and subsequently eliminate them from their niches in the subventricular zone (SVZ).Methods We infused the right lateral ventricle of adult mice brain with 2% Ara-C using four different paradigms—1: one week; 2: two weeks; 3, 4: two weeks with an infusion gap of 6 and 12 h on day 7. Neurosphere assay (NSA), neural colony-forming cell assay (N-CFCA) and immunofluorescent staining were used to assess depletion of NSCs from the SVZ.ResultsNeurosphere formation dramatically decreased in all paradigms immediately after Ara-C infusion. Reduction in neurosphere formation was more pronounced in the 3rd and 4th paradigms. Interestingly 1 week after Ara-C infusion, neurosphere formation recovered toward control values implying the presence of NSCs in the harvested SVZ tissue. Unexpectedly, N-CFCA in the 3rd paradigm, as one of the most effective paradigms, did not result in formation of NSC-derived colonies (colonies >2 mm) even from SVZs harvested 1 week after completion of Ara-C infusion. However, formation of big colonies with serial passaging capability, again confirmed the presence of NSCs.Conclusions Overall, these data suggest Ara-C kill paradigms with infusion gaps deplete NSCs in the SVZ more efficiently but the niches would repopulate even after the most vigorous kill paradigm used in this study.
    Brain and Behavior 10/2015; DOI:10.1002/brb3.404 · 2.24 Impact Factor
  • Source
    • "Similarly, it has been proposed recently that NSCs in the adult SEZ move from an ependymal niche to a vascular niche as they become activated (Kokovay et al. 2010). Interestingly, a6 integrin, a factor that we found expressed by proliferating NSCs and down-regulated when cells enter quiescence (Supplemental Table S1), is required for the binding of NSCs to endothelial cells in the SEZ (Shen et al. 2008). Expression of different repertoires of adhesion molecules, ECM proteins , and ECM receptors by quiescent and activated NSCs is therefore likely to promote or facilitate their interactions with different niche cells and hence play an important role in their exposure to different signaling environments as well as influence how these cells respond to such signals (Kerever et al. 2007; Riquelme et al. 2008; Hynes 2009). "

  • Source
    • "The vasculature may be a critical niche compartment for stem cells in the adult SVZ (Goldberg and Hirschi, 2009; Quaegebeur et al., 2011). The SVZ is extensively vascularized by a rich plexus of blood vessels (Ihrie and Alvarez-Buylla, 2011; Shen et al., 2008; Tavazoie et al., 2008), and the central SVZ has large blood vessels that originate from the ventral aspect (Dorr et al., 2007; Shen et al., 2008). Among the soluble factors released from blood vessels (Goldberg and Hirschi, 2009; Shen et al., 2004), CXCL12/CXCR4 signaling may be involved in the accumulation of microglia in the center plane because microglia express CXCR4 and are recruited in the developing cerebral cortex by CXCL12/CXCR4 signaling (Arno et al., 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: This review summarizes and organizes the literature concerning the effects of microglia on neurogenesis, particularly focusing on the subgranular zone (SGZ) of the hippocampus and subventricular zone (SVZ) of the lateral ventricles, in which the neurogenic potential is progressively restricted during the life of the organism. A comparison of microglial roles in neurogenesis in these two regions indicates that microglia regulate neurogenesis in a temporally and spatially specific manner. Microglia may also sense signals from the surrounding environment and have regulatory effects on neurogenesis. We speculate microglia function as a hub for the information obtained from the inner and outer brain regions for regulating neurogenesis. GLIA 2015. © 2015 The Authors. Glia Published by Wiley Periodicals, Inc.
    Glia 05/2015; 63(8). DOI:10.1002/glia.22858 · 6.03 Impact Factor
Show more