Setting the conditions for efficient, robust and reproducible generation of functionally active neurons from adult subventricular zone-derived neural stem cells

D Goffredo, L Conti, F Di Febo, G Biella, A Tosoni, G Vago, I Biunno, A Moiana, D Bolognini, M Toselli, E Cattaneo

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Although new culture conditions enable homogeneous and long-term propagation of radial glia-like neural stem (NS) cells in monolayer and serum-free conditions, the efficiency of the conversion of NS cells into terminally differentiated, functionally mature neurons is relatively limited and poorly characterized. We demonstrate that NS cells derived from adult mouse subventricular zone robustly develop properties of mature neurons when exposed to an optimized neuronal differentiation protocol. A high degree of cell viability was preserved. At 22 days in vitro, most cells (65%) were microtubule-associated protein 2(+) and coexpressed gamma-aminobutyric acid (GABA), GAD67, calbindin and parvalbumin. Nearly all neurons exhibited sodium, potassium and calcium currents, and 70% of them fired action potentials. These neurons expressed functional GABA(A) receptors, whereas activable kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartic acid receptors were present in approximately 80, 30 and 2% of cells, respectively. Antigenic and functional properties were efficiently and reliably reproduced across experiments and cell passages (up to 68). This is the first report showing a consistent and reproducible generation of large amounts of neurons from long-term passaged adult neural stem cells. Remarkably, the neuronal progeny carries a defined set of antigenic, biochemical and functional characteristics that make this system suitable for studies of NS cell biology as well as for genetic and chemical screenings.
Original languageEnglish
Pages (from-to)1847-1856
Number of pages10
JournalCell Death and Differentiation
Volume15
Issue number12
Early online date12 Sep 2008
DOIs
Publication statusPublished - Dec 2008

Keywords

  • Action Potentials
  • Animals
  • Astrocytes
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cell Proliferation
  • Cell Shape
  • Cerebral Ventricles
  • Ion Channel Gating
  • Mice
  • Neurons
  • Potassium Channels
  • Receptors, GABA
  • Receptors, Glutamate
  • Reproducibility of Results
  • Sodium Channels
  • Stem Cells
  • Time Factors
  • gamma-Aminobutyric Acid

Fingerprint Dive into the research topics of 'Setting the conditions for efficient, robust and reproducible generation of functionally active neurons from adult subventricular zone-derived neural stem cells'. Together they form a unique fingerprint.

  • Cite this

    Goffredo, D., Conti, L., Di Febo, F., Biella, G., Tosoni, A., Vago, G., Biunno, I., Moiana, A., Bolognini, D., Toselli, M., & Cattaneo, E. (2008). Setting the conditions for efficient, robust and reproducible generation of functionally active neurons from adult subventricular zone-derived neural stem cells. Cell Death and Differentiation, 15(12), 1847-1856. https://doi.org/10.1038/cdd.2008.118