Differing in vitro survival dependency of mouse and rat NG2+ oligodendroglial progenitor cells.
NG2 chondroitin sulfate proteoglycan is a surface marker of oligodendroglial progenitor cells (OPCs) in various species. In contrast to well-studied rat OPCs, however, we found that purified mouse NG2 surface positive cells (NG2(+) cells) require additional activation of cyclic AMP (cAMP) signaling for survival in a medium containing 30% B104 neuroblastoma conditioned medium supplemented with fibroblast growth factor-2 (B104CM+FGF2), whereas B104CM+FGF2 alone is sufficient for survival and selective proliferation of rat OPCs. After induction of in vitro differentiation, more than 90% of mouse NG2(+) cells became O4-positive, and a majority expressed myelin basic protein by 5 day of differentiation, which confirmed the identity of isolated mouse NG2(+) cells as OPCs. In comparison to rat OPCs, mouse OPCs in B104CM+FGF2 were less motile, and demonstrated lower basal phosphorylation levels of ERK1/2 and cAMP response element-binding protein (CREB) and a higher incidence of apoptosis mediated by the intrinsic pathway. Transient up-regulation of cAMP-CREB signaling partially inhibited apoptosis of mouse OPCs independently of the ERK pathway. This study demonstrates a difference in trophic requirements between mouse and rat OPCs, with an essential role for cAMP signaling to preserve viability of mouse OPCs.
Horiuchi
Makoto
M
Department of Neurology, University of California, Davis, School of Medicine, Sacramento, California, USA.
Lindsten
Tullia
T
Pleasure
David
D
Itoh
Takayuki
T
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D016380:Brain Tissue Transplantation / Q000379:methods; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003470:Culture Media / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D015415:Biomarkers; D003470:Culture Media; D000242:Cyclic AMP; D017362:Cyclic AMP Response Element-Binding Protein; D016222:Fibroblast Growth Factor 2; D004676:Myelin Basic Protein; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C492004:Creb1 protein, mouse