Contribution of Extracellular Matrix Component Landscapes in the Adult Subventricular Zone to the Positioning of Neural Stem/Progenitor Cells

Abstract

Neurogenesis persists in restricted regions of the adult brain, including the subventricular zone (SVZ). Adult neural stem cells (NSCs) in the SVZ proliferate and give rise to new neurons and glial cells depending on intrinsic and environmental cues. Among the multiple factors that contribute to the chemical, physical, and mechanical components of the neurogenic niche, we focused on the composition of the extracellular matrix (ECM) of vasculature and fractones in the SVZ. The SVZ consists of ECM-rich blood vessels and fractones during development and adulthood, and adult neural stem/progenitor cells (NS/PCs) preferentially attach to the laminin-rich basal lamina. To examine the ECM preference of adult NS/PCs, we designed a competition assay using cell micropatterning. Although both laminin and collagen type IV, which are the main components of basal lamina, act as physical scaffolds, adult NS/PCs preferred to adhere to laminin over collagen type IV. Interestingly, the ECM preference of adult NS/ PCs could be manipulated by chemokines such as stromal-derived factor 1 (SDF1) and α6 integrin. As SDF1 re-routes NSCs and their progenitors toward the injury site after brain damage, these results suggest that the alteration in ECM preferences may provide a molecular basis for contextdependent NS/PC positioning.

Perlecan, A Multi-Functional, Cell-Instructive, Matrix-Stabilizing Proteoglycan With Roles in Tissue Development Has Relevance to Connective Tissue Repair and Regeneration

“…Perlecan has critical roles in basement membrane in the blood brain barrier and important roles in NMJ assembly and function (Figures 5, 6). Perlecan-FGF-2 interactions in the neural stem cell niche (fractone) regulate the survival, proliferation and differentiation of neuroprogenitor stem cell populations in the sub-ventricular and dentate gyrus of the hippocampus (Kerever et al, 2007;Douet et al, 2013;Kerever et al, 2014;Mercier, 2016;Kerever and Arikawa-Hirasawa, 2021;Kim et al, 2021).…”

Regulation of neural stem cell proliferation and survival by protein arginine methyltransferase 1

“…Thus, we performed qRT-PCR of PRMT1-deficient brains at E14, when the normal distribution of NSC was confirmed ( Figure 1C ). A major extracellular matrix protein, laminin, has been reported to provide signaling cues for NSC adhesion and proliferation ( Li et al, 2014 ; Kim et al, 2021 ). Laminin is a heterotrimeric protein, and astrocytes express laminins-111 (α1β1γ1) and -211 (α2β1γ1) ( Yao et al, 2014 ).…”

Mimicking the neural stem cell niche: An engineer’s view of cell: material interactions

“…In this regard, Bergström et al (2014) confirmed that mRNA pattern encoding collagen I-binding integrins differs from postnatal to adulthood, especially integrin α1, α2 and integrin α11 and that is why adult human-derived neural stem cells cannot adhere to the collagen I-treated substrates while postnatal ones can. In studying the vascular basement membrane protein assembly for the neurogenic niche, Kim et al (2021) illustrated that progenitor cells were less likely to adhere to collagen IV-overlaid laminin substrates versus lamininoverlaid collagen IV, suggesting the importance of laminin recognition within the niche. In pathological conditions, investigating laminin and collagen IV organization could be something interesting to study; however, there are still very limited studies on the effect of collagen IV on neural stem cell behavior.…”