Differentiation of the immortalized adult neuronal progenitor cell line HC2S2 into neurons by regulatable suppression of the v-myc oncogene.
A regulatable retroviral vector in which the v-myc oncogene is driven by a tetracycline-controlled transactivator and a human cytomegalovirus minimal promoter fused to a tet operator sequence was used for conditional immortalization of adult rat neuronal progenitor cells. A single clone, HC2S2, was isolated and characterized. Two days after the addition of tetracycline, the HC2S2 cells stopped proliferating, began to extend neurites, and expressed the neuronal markers tau, NeuN, neurofilament 200 kDa, and glutamic acid decarboxylase in accordance with the reduced production of the v-myc oncoprotein. Differentiated HC2S2 cells expressed large sodium and calcium currents and could fire regenerative action potentials. These results suggest that the suppression of the v-myc oncogene may be sufficient to make proliferating cells exit from cell cycles and induce terminal differentiation. The HC2S2 cells will be valuable for studying the differentiation process of neurons.
Hoshimaru
M
M
Laboratory of Genetics, The Salk Institute for Biological Studies, San Diego, CA 92186-5800, USA.
Ray
J
J
Sah
D W
DW
Gage
F H
FH
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D003587:Cytomegalovirus / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005813:Genes, Synthetic; D005814:Genes, Viral; D016259:Genes, myc; D005822:Genetic Vectors; D006624:Hippocampus / Q000166:cytology; D008969:Molecular Sequence Data; D008980:Moloney murine sarcoma virus / Q000235:genetics; D016501:Neurites / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology*; D016274:Oncogene Protein p55(v-myc) / Q000096:biosynthesis / Q000502:physiology; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D018139:Simplexvirus / Q000235:genetics; D013752:Tetracycline / Q000494:pharmacology; D015533:Transcriptional Activation
D016274:Oncogene Protein p55(v-myc); D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D013752:Tetracycline