Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells

Cell. 1999 Mar 5;96(5):737-49. doi: 10.1016/s0092-8674(00)80583-8.

Abstract

Multipotent and self-renewing neural stem cells have been isolated in culture, but equivalent cells have not yet been prospectively identified in neural tissue. Using cell surface markers and flow cytometry, we have isolated neural crest stem cells (NCSCs) from mammalian fetal peripheral nerve. These cells are phenotypically and functionally indistinguishable from NCSCs previously isolated by culturing embryonic neural tube explants. Moreover, in vivo BrdU labeling indicates that these stem cells self-renew in vivo. NCSCs freshly isolated from nerve tissue can be directly transplanted in vivo, where they generate both neurons and glia. These data indicate that neural stem cells persist in peripheral nerve into late gestation by undergoing self-renewal. Such persistence may explain the origins of some PNS tumors in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / pharmacology
  • Cell Differentiation / drug effects
  • Cell Division
  • Cell Lineage
  • Cell Separation / methods
  • Cells, Cultured
  • Flow Cytometry
  • Gestational Age
  • Glycoproteins / pharmacology
  • Neural Crest / cytology*
  • Neuregulins
  • Neuroectodermal Tumors, Primitive / embryology
  • Neuroglia / cytology
  • Neurons / cytology
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / cytology*
  • Sciatic Nerve / embryology
  • Stem Cell Transplantation
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Transforming Growth Factor beta*

Substances

  • BMP2 protein, human
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Glycoproteins
  • Neuregulins
  • Transforming Growth Factor beta