Single factors direct the differentiation of stem cells from the fetal and adult central nervous system.
Identifying the signals that regulate stem cell differentiation is fundamental to understanding cellular diversity in the brain. In this paper we identify factors that act in an instructive fashion to direct the differentiation of multipotential stem cells derived from the embryonic central nervous system (CNS). CNS stem cell clones differentiate to multiple fates: neurons, astrocytes, and oligodendrocytes. The differentiation of cells in a clone is influenced by extracellular signals: Platelet-derived growth factor (PDGF-AA, -AB, and -BB) supports neuronal differentiation. In contrast, ciliary neurotrophic factor and thyroid hormone T3 act instructively on stem cells to generate clones of astrocytes and oligodendrocytes, respectively. Adult stem cells had remarkably similar responses to these growth factors. These results support a simple model in which transient exposure to extrinsic factors acting through known pathways initiates fate decisions by multipotential CNS stem cells.
Johe
K K
KK
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hazel
T G
TG
Muller
T
T
Dugich-Djordjevic
M M
MM
McKay
R D
RD
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002454:Cell Differentiation; D002490:Central Nervous System / Q000166:cytology*; D020934:Ciliary Neurotrophic Factor; D002999:Clone Cells; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000166:cytology; D009836:Oligodendroglia / Q000166:cytology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D051381:Rats; D013234:Stem Cells / Q000166:cytology*; D014284:Triiodothyronine / Q000502:physiology
D020934:Ciliary Neurotrophic Factor; D009419:Nerve Tissue Proteins; D010982:Platelet-Derived Growth Factor; D014284:Triiodothyronine