Chemokine receptor CXCR4 signaling modulates the growth factor-induced cell cycle of self-renewing and multipotent neural progenitor cells

Meizhang Li, Cathleen J. Chang, Justin D. Lathia, Li Wang, Holly L. Pacenta, Anne Cotleur, Richard M. Ransohoff

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

CXC chemokine receptor CXCR4 is expressed in vitro in both human and rodent adult neural progenitor cells (NPCs). It has been suggested that the CXCL12-CXCR4 axis potentially enhances the proliferation of NPCs. However, whether CXCR4 is expressed in the neural stem cells (NSCs), a subset of self-renewing and multipotent NPCs, and whether CXCR4 signaling is directly required for their proliferation are not clear. In this study, we report that CXCR4 is expressed in a subpopulation of NPCs in the early embryonic ventricular zone. In studies of a CXCR4eGFP bacterial artificial chromosomal (BAC) transgenic mouse line, we further isolated NPCs from E12.5 transgenic telencephalon and GFP+ cells demonstrated self-renewal and multipotency in neurosphere assays in vitro. Consistent with these observations, we enriched GFP+/CXCR4+ cells by fluorescence activated cell sorting (FACS) with either CXCR4 antibody 12G5 or GFP. Furthermore, we observed that CXCL12 alone did not activate the self-renewal of NPCs or increase the proliferation of NPCs that are induced by bFGF/EGF. However, we found that blocking CXCR4 receptor with antagonist AMD3100 impaired the bFGF/EGF-induced expansion of GFP+ NPCs through modulating their cell cycling. In addition, AMD3100 treatment of pregnant mice reduced the generation of neurospheres from E12.5 embryos. Our data suggest that CXCR4 is a potential cell surface marker for early embryonic NSCs and modulates growth-factor signaling.

Original languageEnglish (US)
Pages (from-to)108-118
Number of pages11
JournalGLIA
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Keywords

  • CXCL12
  • CXCR4
  • Cell cycling
  • Neural progenitor cells
  • Proliferation

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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