4.8 Article

Adult hippocampal neural stem and progenitor cells regulate the neurogenic niche by secreting VEGF

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1422448112

Keywords

adult neurogenesis; vascular endothelial growth factor; stem cell; hippocampus; neural precursor

Funding

  1. NIH [AG045034]
  2. Department of Veterans Affairs
  3. postdoctoral National Research Service Award from the National Institute of Neurological Disorders and Stroke
  4. California Institute for Regenerative Medicine Bridges to Stem Cell Research Award [TB1-01190]
  5. Stanford Summer Research Program

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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.

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