Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity.
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.
Kawasaki
H
H
Department of Medical Embryology and Neurobiology, Institute for Frontier Medical Sciences, Kyoto University, Japan.
Mizuseki
K
K
Nishikawa
S
S
Kaneko
S
S
Kuwana
Y
Y
Nakanishi
S
S
Nishikawa
S I
SI
Sasai
Y
Y
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism* / Q000494:pharmacology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D046508:Culture Techniques / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D029867:Xenopus Proteins
D000943:Antigens, Differentiation; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D016895:Culture Media, Serum-Free; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine