Endogenous IGF-1 regulates the neuronal differentiation of adult stem cells.
Stem cells from the adult forebrain of mice were stimulated to form clones in vitro using fibroblast growth factor-2 (FGF-2). At concentrations above 10 ng/ml of FGF-2, very few clones gave rise to neurons; however, if FGF-2 was removed after 5 days, 20-30% of clones subsequently gave rise to neurons. The number of neuron-containing clones and the number of neurons per clone was significantly enhanced, if insulin-like growth factor (IGF)-1 or heparin were added subsequent to FGF-2 removal. The spontaneous production of neurons after FGF-2 removal was shown to be due to endogenous IGF-1, since antibodies to IGF-1 and an IGF-1 binding protein totally inhibited neuronal production. Similarly, these reagents also abrogated the neuron-promoting effects of heparin. Thus, it appears that endogenous IGF-1 may be a major regulator of stem cell differentiation into neurons. Furthermore, it was found that high levels of IGF-1 or insulin promoted the maturation and affected the neurotransmitter phenotype of the neurons generated.
Brooker
G J
GJ
The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
Kalloniatis
M
M
Russo
V C
VC
Murphy
M
M
Werther
G A
GA
Bartlett
P F
PF
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016207:Cytokines; D018971:Insulin-Like Growth Factor Binding Protein 2; D009414:Nerve Growth Factors; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D006493:Heparin