Analysis of Stem Cell Lineage Progression in the Neonatal Subventricular Zone Identifies EGFR+/NG2 Cells as Transit-Amplifying Precursors

Authors


  • Author contributions: T.C., K.O., and C.P.B.: collection of data and analysis, data interpretation, manuscript writing; T.F.: collection and analysis of the data; C.M., G.H.-W., K.W., and V.E.: collection of the data; F.C.: conception and design, data analysis and interpretation, manuscript writing. T.C. and K.O. contributed equally to this article.

  • First published online in STEM CELLSExpress March 26, 2009

Abstract

In the adult subventricular zone (SVZ), astroglial stem cells generate transit-amplifying precursors (TAPs). Both stem cells and TAPs form clones in response to epidermal growth factor (EGF). However, in vivo, in the absence of sustained EGF receptor (EGFR) activation, TAPs divide a few times before differentiating into neuroblasts. The lack of suitable markers has hampered the analysis of stem cell lineage progression and associated functional changes in the neonatal germinal epithelium. Here we purified neuroblasts and clone-forming precursors from the neonatal SVZ using expression levels of EGFR and polysialylated neural cell adhesion molecule (PSANCAM). As in the adult SVZ, most neonatal clone-forming precursors did not express the neuroglia proteoglycan 2 (NG2) but displayed characteristics of TAPs, and only a subset exhibited antigenic characteristics of astroglial stem cells. Both precursors and neuroblasts were PSANCAM+; however, neuroblasts also expressed doublecortin and functional voltage-dependent Ca2+ channels. Neuroblasts and precursors had distinct outwardly rectifying K+ current densities and passive membrane properties, particularly in precursors contacting each other, because of the contribution of gap junction coupling. Confirming the hypothesis that most are TAPs, cell tracing in brain slices revealed that within 2 days the majority of EGFR+ cells had exited the cell cycle and differentiated into a progenitor displaying intermediate antigenic and functional properties between TAPs and neuroblasts. Thus, distinct functional and antigenic properties mark stem cell lineage progression in the neonatal SVZ. STEM CELLS 2009;27:1443–1454

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