Nestin-GFP transgene reveals neural precursor cells in adult skeletal muscle

PLoS One. 2011 Feb 3;6(2):e16816. doi: 10.1371/journal.pone.0016816.

Abstract

Background: Therapy for neural lesions or degenerative diseases relies mainly on finding transplantable active precursor cells. Identifying them in peripheral tissues accessible for biopsy, outside the central nervous system, would circumvent the serious immunological and ethical concerns impeding cell therapy.

Methodology/principal findings: In this study, we isolated neural progenitor cells in cultured adult skeletal muscle from transgenic mice in which nestin regulatory elements control GFP expression. These cells also expressed the early neural marker Tuj1 and light and heavy neurofilament but not S100β, indicating that they express typical neural but not Schwann cell markers. GFP+/Tuj1+ cells were also negative for the endothelial and pericyte markers CD31 and α-smooth muscle actin, respectively. We established their a) functional response to glutamate in patch-clamp recordings; b) interstitial mesenchymal origin; c) replicative capacity; and d) the environment necessary for their survival after fluorescence-activated cell sorting.

Conclusions/significance: We propose that the decline in nestin-GFP expression in muscle progenitor cells and its persistence in neural precursor cells in muscle cultures provide an invaluable tool for isolating a population of predifferentiated neural cells with therapeutic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Aging / physiology
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Tracking / methods
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Green Fluorescent Proteins / genetics*
  • Green Fluorescent Proteins / metabolism
  • Green Fluorescent Proteins / physiology
  • Intermediate Filament Proteins / genetics*
  • Intermediate Filament Proteins / metabolism
  • Intermediate Filament Proteins / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology
  • Nestin
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / physiology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / physiology
  • Transgenes / physiology*

Substances

  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins