Pigment epithelium-derived factor is a niche signal for neural stem cell renewal

• Published in: Nature neuroscience Vol. 9; no. 3; pp. 331 - 339
• Main Authors: Fariñas, Isabel, Ramírez-Castillejo, Carmen, Sánchez-Sánchez, Francisco, Andreu-Agulló, Celia, Ferrón, Sacri R, Aroca-Aguilar, J Daniel, Sánchez, Pilar, Mira, Helena, Escribano, Julio
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.03.2006
• Subjects: Animals; Cell cycle; Cell Cycle - drug effects; Cell Cycle - physiology; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Division - drug effects; Cell Division - physiology; Cell Proliferation - drug effects; Cells, Cultured; Cellular signal transduction; Cercopithecus aethiops; COS Cells; Endothelium, Vascular - metabolism; Endothelium, Vascular - secretion; Ependyma - cytology; Ependyma - drug effects; Ependyma - metabolism; Epithelium; Extracellular matrix; Eye Proteins - metabolism; Eye Proteins - pharmacology; Growth factors; Hippocampus - cytology; Hippocampus - metabolism; Humans; Injections, Intraventricular; Lateral Ventricles - cytology; Lateral Ventricles - metabolism; Mice; Nerve Growth Factors - metabolism; Nerve Growth Factors - pharmacology; Neurogenesis; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons - cytology; Neurons - metabolism; Physiological aspects; Proteins; Serpins - metabolism; Serpins - pharmacology; Signal Transduction - drug effects; Signal Transduction - physiology; Stem cells; Stem Cells - drug effects; Stem Cells - metabolism; Telencephalon - cytology; Telencephalon - drug effects; Telencephalon - metabolism; Spain
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn1657

Adult stem cells are characterized by self-renewal and multilineage differentiation, and these properties seem to be regulated by signals from adjacent differentiated cell types and by extracellular matrix molecules, which collectively define the stem cell "niche." Self-renewal is essential for the lifelong persistence of stem cells, but its regulation is poorly understood. In the mammalian brain, neurogenesis persists in two germinal areas, the subventricular zone (SVZ) and the hippocampus, where continuous postnatal neuronal production seems to be supported by neural stem cells (NSCs). Here we show that pigment epithelium-derived factor (PEDF) is secreted by components of the murine SVZ and promotes self-renewal of adult NSCs in vitro. In addition, intraventricular PEDF infusion activated slowly dividing stem cells, whereas a blockade of endogenous PEDF decreased their cycling. These data demonstrate that PEDF is a niche-derived regulator of adult NSCs and provide evidence for a role for PEDF protein in NSC maintenance.