A Mesenchymal-Like ZEB1+ Niche Harbors Dorsal Radial Glial Fibrillary Acidic Protein-Positive Stem Cells in the Spinal Cord§

Authors

  • Jean-Charles Sabourin,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
  • Karin B. Ackema,

    1. Growth & Development, Biozentrum, University of Basel, Basel, Switzerland
    Search for more papers by this author
  • David Ohayon,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
  • Pierre-Olivier Guichet,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
  • Florence E. Perrin,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
  • Alain Garces,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
  • Chantal Ripoll,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
  • Jeroen Charité,

    1. Department of Cell Biology, Erasmus Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Lionel Simonneau,

    1. Laboratoire interdisciplinaire de recherche en didactique et formation, University Montpellier, Montpellier, France
    Search for more papers by this author
  • H. Kettenmann,

    1. Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany
    Search for more papers by this author
  • Azel Zine,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
  • Alain Privat,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
    • A.P. and J.P.H. contributed equally to this work.

  • Jean Valmier,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
  • Alexandre Pattyn,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
  • Jean-Philippe Hugnot

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    • Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France
    Search for more papers by this author
    • A.P. and J.P.H. contributed equally to this work.

    • Tel: 00 33 4 99 63 60 08; Fax: 00 33 4 99 63 60 20


  • Author contributions: J.C.S., K.B.A. P.O.G., F.E.P., and C.R.: conception and design; D.O., J.C., L.S., H.K., A.Z., and A.P.: provision of study material; A.G.: collection and/or assembly of data; A.P. and J.V.: financial support; J.P. H.: conception and design, manuscript writing, final approval of manuscript.

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

  • §

    First published online in STEM CELLS EXPRESS September 25, 2009.

Abstract

In humans and rodents the adult spinal cord harbors neural stem cells located around the central canal. Their identity, precise location, and specific signaling are still ill-defined and controversial. We report here on a detailed analysis of this niche. Using microdissection and glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP) transgenic mice, we demonstrate that neural stem cells are mostly dorsally located GFAP+ cells lying ependymally and subependymally that extend radial processes toward the pial surface. The niche also harbors doublecortin protein (Dcx)+ Nkx6.1+ neurons sending processes into the lumen. Cervical and lumbar spinal cord neural stem cells maintain expression of specific rostro-caudal Hox gene combinations and the niche shows high levels of signaling proteins (CD15, Jagged1, Hes1, differential screening-selected gene aberrative in neuroblastoma [DAN]). More surprisingly, the niche displays mesenchymal traits such as expression of epithelial-mesenchymal-transition zinc finger E-box-binding protein 1 (ZEB1) transcription factor and smooth muscle actin. We found ZEB1 to be essential for neural stem cell survival in vitro. Proliferation within the niche progressively ceases around 13 weeks when the spinal cord reaches its final size, suggesting an active role in postnatal development. In addition to hippocampus and subventricular zone niches, adult spinal cord constitutes a third central nervous system stem cell niche with specific signaling, cellular, and structural characteristics that could possibly be manipulated to alleviate spinal cord traumatic and degenerative diseases. STEM CELLS 2009;27:2722–2733

Ancillary