Symmetric Expansion of Neural Stem Cells from the Adult Olfactory Bulb Is Driven by Astrocytes Via WNT7A§

Authors

  • Mireia Moreno-EstellÉs,

    1. Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, CNM, Instituto de Salud Carlos III, Majadahonda, Spain
    Search for more papers by this author
  • Pilar GonzÁlez-Gómez,

    1. Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, CNM, Instituto de Salud Carlos III, Majadahonda, Spain
    Search for more papers by this author
  • Rafael Hortigüela,

    1. Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, CNM, Instituto de Salud Carlos III, Majadahonda, Spain
    Search for more papers by this author
  • María Díaz-Moreno,

    1. Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, CNM, Instituto de Salud Carlos III, Majadahonda, Spain
    Search for more papers by this author
  • Juana San Emeterio,

    1. Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, CNM, Instituto de Salud Carlos III, Majadahonda, Spain
    Search for more papers by this author
  • Carvalho AL,

    1. Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, CNM, Instituto de Salud Carlos III, Majadahonda, Spain
    Search for more papers by this author
  • Isabel FariÑas,

    1. Departamento de Biología Celular y Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Universidad de Valencia, Burjassot, Spain
    Search for more papers by this author
  • Helena Mira

    Corresponding author
    1. Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, CNM, Instituto de Salud Carlos III, Majadahonda, Spain
    • Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda—Pozuelo, Km. 2.2, Majadahonda, 28220 Madrid, Spain
    Search for more papers by this author
    • Telephone: +34-91-822-3271; Fax: +34-91-822-3269


  • Author contributions: M.M.-E.: conception and design, collection and/or assembly of data, and data analysis and interpretation; R.H., P.G.-G., M.D.-M., J.S.E., and A.L.C.: collection and/or assembly of data; I.F.: conception and design and financial support; H.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, financial support, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS September 17, 2012.

Abstract

Adult neural stem cells (NSCs) located in the subventricular zone (SVZ) persistently produce new neurons destined to the olfactory bulb (OB). Recent research suggests that the OB is also a source of NSCs that remains largely unexplored. Using single/dual-labeling procedures, we address the existence of NSCs in the innermost layers of the OB. In vivo, these cells are more quiescent that their SVZ counterparts, but after in vitro expansion, they behave similarly. Self-renewal and proliferation assays in co-culture with niche astrocytes indicate that OB-glia restricts NSC activity whereas SVZ-glia has the opposite effect. Gene expression profiling identifies WNT7A as a key SVZ-glial factor lacking in OB-glia that enhances self-renewal, thereby improving the propagation of OB-NSC cultures. These data demonstrate that region-specific glial factors account for in vivo differences in NSC activity and point to WNT7A as a tool that may be instrumental for the NSC expansion phase that precedes grafting. STEM CELLS 2012;30:2796–2809

Ancillary