The Paracrine Neural Stem Cell Niche: New Actors in the Play

Abstract

The neural stem cell (NSC) niche has been partially characterized and defined in the mammalian brain. Two adult niches have been identified: the dentate gyrus (DG) in the hippocampus and the subventricular zone (SVZ). Neural stem cells reside in these microenvironments near to vascular cells, with which they communicate through paracrine factors. This review summarizes the latest vascular paracrine factors identified to play a role in the NSC niche. Soluble factors released by the vasculature, such as pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF), betacellulin (BTC), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, and Notch ligand Jagged 1, regulate NSC behavior in the niche. New paracrine factors, like APP and EGFL-7, have been recently identified as part of the NSC niche. The choroid plexus of the lateral ventricle (LVCP) has also been identified as a key regulator of the NSC niche. Finally, exosomes containing proteins or microRNAs are released by different cell types in the NSC niche and are considered to play a role in the regulation of NSCs. The niche vasculature and the choroid plexus are key components of the NSC niche that determine NSC fate by releasing paracrine factors, either directly or contained in exosomes. Understanding the complexity of the microenvironment and NSC niche cytoarchitecture will help to unveil the regulatory mechanisms that control NSC biology.