A novel oligodendrocyte cell line OLP6 shows the successive stages of oligodendrocyte development: late progenitor, immature and mature stages.
The successive stages of development from oligodendrocyte progenitor to mature oligodendrocyte have been investigated in detail by using stage-specific antibodies. However, no cell lines are available that show stepwise differentiation from oligodendrocyte progenitors to mature oligodendrocytes. Here we show the establishment of an immortalized oligodendrocyte cell line, OLP6, from adult transgenic rats harboring the temperature-sensitive simian virus 40 large T-antigen gene. The OLP6 cells had a fibroblastic morphology and continuously proliferated at 33 degrees C. They displayed growth arrest and multipolar morphology when they were cultured at 39 degrees C. They express the oligodendrocytic markers O4, 2'-3'-cyclic-nucleotide 3'-phosphodiesterase, galactocerebroside and second endothelial differentiation gene receptor-2 at 39 degrees C. The OLP6 cells underwent apoptosis upon serum withdrawal at 39 degrees C. Lysophosphatidic acid inhibited this apoptosis and promoted the expression of myelin basic protein. These results demonstrate that the activation of endothelial differentiation gene receptor-2 exerts anti-apoptosis and myelinogenesis effects on the OLP6 cells. Taken together, the OLP6 cells in the late oligodendrocyte progenitor stage can progress to the immature oligodendrocyte stage by shifting culture temperature. Furthermore, lysophosphatidic acid promoted the maturation of OLP6 cells in the immature oligodendrocyte stage. Such OLP6 cells should provide a potent model system for studying the precise mechanism involved in stepwise differentiation of oligodendrocytes.
Matsushita
T
T
Molecular Medicine Laboratories Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585 Japan.
Amagai
Y
Y
Soga
T
T
Terai
K
K
Obinata
M
M
Hashimoto
S
S
D000818:Animals; D030801:Animals, Genetically Modified; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D016922:Cellular Senescence; D007150:Immunohistochemistry; D008246:Lysophospholipids / Q000494:pharmacology; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D013539:Simian virus 40 / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D013696:Temperature
D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid