Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells

Science. 2004 May 28;304(5675):1338-40. doi: 10.1126/science.1095505. Epub 2004 Apr 1.

Abstract

Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes 1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / physiology
  • Cattle
  • Cell Adhesion
  • Cell Communication*
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cell Lineage
  • Cells, Cultured
  • Cerebral Cortex / embryology
  • Clone Cells / physiology
  • Coculture Techniques
  • Embryo, Mammalian / cytology
  • Endothelial Cells / cytology
  • Endothelial Cells / physiology*
  • Endothelium, Vascular / cytology
  • Fibroblast Growth Factor 2 / pharmacology
  • Mice
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / physiology
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / physiology
  • Neurons / cytology
  • Neurons / physiology*
  • Oligodendroglia / cytology
  • Oligodendroglia / physiology
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / physiology*

Substances

  • Fibroblast Growth Factor 2