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.

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    • "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). "
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    • "integrins) on their surface that interact with components (members of the laminin family as well as collagen IV, agrin, nidogen, perlecan) of the surrounding basal lamina (Erickson and Couchman, 2000). This interaction helps anchor and orient stem cells in the niche (Shen et al., 2008). Other components in the matrix, like heparan sulfate proteoglycans (HSPG), bind mitogens like FGF-2 (Kerever et al., 2007) while growth factors like NGF can bind other laminins present in the niche (Bhang et al., 2009; Sun et al., 2009). "
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    ABSTRACT: Neural stem cells (NSCs) critical for the continued production of new neurons and glia are sequestered in distinct areas of the brain called stem cell niches. Until recently, only two forebrain sites, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus, have been recognized adult stem cell niches (Alvarez-Buylla and Lim, 2004; Doetsch et al., 1999a, 1999b; Doetsch, 2003a, 2003b; Lie et al., 2004; Ming and Song, 2005). Nonetheless, the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury (Barnabé-Heider et al., 2010; Carlén et al., 2009; Decimo et al., 2012; Lin et al., 2015; Lindvall and Kokaia, 2008; Robins et al., 2013) or other inductive stimuli (Bennett et al., 2009; Cunningham et al., 2012; Decimo et al., 2011; Kokoeva et al., 2007, 2005; Lee et al., 2012; Migaud et al., 2010; Pencea et al., 2001b; Sanin et al., 2013; Suh et al., 2007; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). This review focuses on the role of these novel and classic brain niches in maintaining adult neurogenesis and gliogenesis in response to normal physiological and injury-related pathological cues. Copyright © 2015. Published by Elsevier B.V.
    Brain research 04/2015; 219. DOI:10.1016/j.brainres.2015.04.029 · 2.84 Impact Factor
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    • "Rapidly dividing type C cells give rise to type A neuroblasts, progenitors that divide as they migrate, usually in cell chains. In the dorsal SVZ, neuroblast chains often run parallel to blood vessels in the direction of the RMS (see Fig. 3: Shen et al., 2008; Tavazoie et al., 2008) and the OB (Snapyan et al., 2009). Upon arrival at the OB, neuroblasts switch to radial migration in order to reach their final destination. "
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    ABSTRACT: In the adult brain, Neural Progenitor Cells (NPCs) reside in the subventricular zone (SVZ) of the lateral ventricles, the dentate gyrus and the olfactory bulb. Following CNS insult, NPCs from the SVZ can migrate along the rostral migratory stream (RMS), a migration of NPCs that is directed by proinflammatory cytokines. Indeed, cells expressing CXCR4 follow a homing signal that ultimately leads to neuronal integration and CNS repair, although such molecules can also promote NPC quiescence. The ligand, SDF1 alpha (or CXCL12) is one of the chemokines secreted at sites of injury that it is known to attract NSC-derived neuroblasts, cells that express CXCR4. In function of its concentration, CXCL12 can induce different responses, promoting NPC migration at low concentrations while favoring cell adhesion via EGF and the alpha 6 integrin at high CXCL12 concentrations. However, the preclinical effectiveness of chemokines and their relationship with NPC mobilization requires further study, particularly with respect to CNS repair. Indeed, NPC migration may also be affected by the release of cytokines or chemokines induced by local inflammation, through autocrine or paracrine mechanisms, as well as through erythropoietin (EPO) or nitric oxide (NO) release. CXCL12 activity requires G-coupled proteins and the availability of its ligand may be modulated by its binding to CXCR7, for which it shows a stronger affinity than for CXCR4. © 2014 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 01/2015; 230(1). DOI:10.1002/jcp.24695 · 3.84 Impact Factor
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