Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling

Cell Stem Cell. 2010 Aug 6;7(2):163-73. doi: 10.1016/j.stem.2010.05.019.

Abstract

Neural progenitor cells (NPCs) in the adult subventricular zone (SVZ) are associated with ependymal and vasculature niches, which regulate stem cell self-renewal and differentiation. Activated Type B stem cells and their progeny, the transit-amplifying type C cells, which express EGFR, are most highly associated with vascular cells, indicating that this niche supports lineage progression. Here, we show that proliferative SVZ progenitor cells home to endothelial cells in a stromal-derived factor 1 (SDF1)- and CXC chemokine receptor 4 (CXCR4)-dependent manner. We show that SDF1 strongly upregulates EGFR and alpha6 integrin in activated type B and type C cells, enhancing their activated state and their ability to bind laminin in the vascular niche. SDF1 increases the motility of type A neuroblasts, which migrate from the SVZ toward the olfactory bulb. Thus, differential responses to SDF1 can regulate progenitor cell occupancy of and exit from the adult SVZ vascular niche.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • B-Lymphocytes / cytology
  • Blood Vessels / cytology
  • Cell Lineage*
  • Cerebral Ventricles / blood supply*
  • Cerebral Ventricles / cytology*
  • Chemokine CXCL12 / metabolism*
  • Chemotaxis*
  • Endothelial Cells / metabolism
  • ErbB Receptors / metabolism
  • Integrins / metabolism
  • Lymphocyte Activation
  • Mice
  • Models, Biological
  • Neurons / cytology
  • Neurons / metabolism
  • Receptors, CXCR4 / metabolism*
  • Signal Transduction*
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Integrins
  • Receptors, CXCR4
  • ErbB Receptors