title: Adult hippocampal neural stem and progenitor cells regulate the neurogenic niche by secreting VEGF.
abstract: The adult hippocampus hosts a population of neural stem and progenitor cells (NSPCs) that proliferates throughout the mammalian life span. To date, the new neurons derived from NSPCs have been the primary measure of their functional relevance. However, recent studies show that undifferentiated cells may shape their environment through secreted growth factors. Whether endogenous adult NSPCs secrete functionally relevant growth factors remains unclear. We show that adult hippocampal NSPCs secrete surprisingly large quantities of the essential growth factor VEGF in vitro and in vivo. This self-derived VEGF is functionally relevant for maintaining the neurogenic niche as inducible, NSPC-specific loss of VEGF results in impaired stem cell maintenance despite the presence of VEGF produced from other niche cell types. These findings reveal adult hippocampal NSPCs as an unanticipated source of an essential growth factor and imply an exciting functional role for adult brain NSPCs as secretory cells.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305; and.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Kirby
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305; and.
authors.forename: Akela A
authors.initials: AA
authors.lastname: Kuwahara
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305; and.
authors.forename: Reanna L
authors.initials: RL
authors.lastname: Messer
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305; and Center for Tissue Regeneration, Repair, and Restoration, Veterans Administration Palo Alto Health Care Systems, Palo Alto, CA 94304 twc@stanford.edu.
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D008568:Memory; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: adult neurogenesis; hippocampus; neural precursor; stem cell; vascular endothelial growth factor