Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity

Neuron. 2000 Oct;28(1):31-40. doi: 10.1016/s0896-6273(00)00083-0.

Abstract

We have identified a stromal cell-derived inducing activity (SDIA) that promotes neural differentiation of mouse ES cells. SDIA accumulates on the surface of PA6 stromal cells and induces efficient neuronal differentiation of cocultured ES cells in serum-free conditions without use of either retinoic acid or embryoid bodies. BMP4, which acts as an antineuralizing morphogen in Xenopus, suppresses SDIA-induced neuralization and promotes epidermal differentiation. A high proportion of tyrosine hydroxylase-positive neurons producing dopamine are obtained from SDIA-treated ES cells. When transplanted, SDIA-induced dopaminergic neurons integrate into the mouse striatum and remain positive for tyrosine hydroxylase expression. Neural induction by SDIA provides a new powerful tool for both basic neuroscience research and therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / metabolism*
  • Antigens, Differentiation / pharmacology
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / pharmacology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Corpus Striatum / cytology
  • Corpus Striatum / metabolism
  • Corpus Striatum / surgery
  • Culture Media, Serum-Free / pharmacology
  • Culture Techniques / methods
  • Dopamine / metabolism*
  • Epidermal Cells
  • Epidermis / drug effects
  • Mesencephalon / cytology
  • Mesencephalon / metabolism*
  • Mesencephalon / surgery
  • Mice
  • Mice, Inbred Strains
  • Neurons / cytology
  • Neurons / metabolism*
  • Neurons / transplantation
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stromal Cells / cytology
  • Stromal Cells / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism
  • Xenopus Proteins

Substances

  • Antigens, Differentiation
  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Culture Media, Serum-Free
  • Xenopus Proteins
  • bmp4 protein, Xenopus
  • Tyrosine 3-Monooxygenase
  • Dopamine