Lines of glial precursor cells immortalised with a temperature-sensitive oncogene give rise to astrocytes and oligodendrocytes following transplantation into demyelinated lesions in the central nervous system.
Immortalised lines of murine glial precursor cells expressing the neomycin resistance gene and a temperature-sensitive mutation of the SV 40 T oncogene were established from cultures of oligodendrocytes and precursor cells infected with a replication-incompetent, helper-free retrovirus. At the permissive temperature (33 degrees C), they could be continually propagated in vitro and cells were present expressing the 04 antigen specific for glial precursor cells and oligodendrocytes. At 38 degrees C, where the expression of the T antigen is down regulated, cell division largely ceased. During early passage in vitro, limited differentiation to a more mature phenotype, as evidenced by expression of GFAP and the oligodendrocyte marker 01 was observed at both 33 degrees C and 38 degrees C. When transplanted into demyelinating lesions in the spinal cords of adult rats early passages of the lines yielded myelin-forming oligodendrocytes and astrocytes. Cells from later passages of the lines although failing to synthesise myelin still associated specifically with the demyelinated axons. These experiments demonstrate the retention of physiological properties of these oncogene-carrying glial cells when transplanted in vivo and suggest that such immortalised populations can be used for the isolation of molecules regulating glial cell function.
Trotter
J
J
Department of Neurobiology, University of Heidelberg, Germany.
Crang
A J
AJ
Schachner
M
M
Blakemore
W F
WF
D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001369:Axons / Q000648:ultrastructure; D015415:Biomarkers / Q000032:analysis; D015139:Blotting, Southern; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis; D004622:Embryo, Mammalian; D016332:Fetal Tissue Transplantation; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D019868:Kanamycin Kinase; D051379:Mice; D008815:Mice, Inbred Strains; D009186:Myelin Sheath / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D009836:Oligodendroglia / Q000166:cytology*; D009857:Oncogenes; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D013539:Simian virus 40 / Q000235:genetics*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013696:Temperature; D014183:Transplantation, Heterologous
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D004247:DNA; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase