Bipotent progenitor cell lines from the human CNS.
Human central nervous system (CNS) cell lines would substantially facilitate drug discovery and basic research by providing a readily renewable source of human neurons. We isolated clonal human CNS cell lines that had been immortalized with a tetracycline (Tc)-responsive v-myc oncogene; addition of Tc to the growth medium suppressed the oncoprotein rapidly and virtually completely, allowing differentiation to proceed. Two classes of bipotent precursor cells were immortalized: the first class had a default differentiation pathway of neurons only, and the second class had a default differentiation pathway of neurons and astrocytes. We found that after exposure to different external signals in vitro, the environment is capable of redirecting the fate of a particular cell, even in the case of the bipotent precursor cell whose default differentiation pathway was neurons only. These data suggest that extrinsic cues can prevail over intrinsic determinants in directing cell fate in the human CNS.
Sah
D W
DW
Signal Pharmaceuticals Incorporated, San Diego, CA 92121, USA. dsah@signalpharm.com
Ray
J
J
Gage
F H
FH
D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology* / Q000196:embryology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002460:Cell Line; D002461:Cell Line, Transformed; D005333:Fetus; D016259:Genes, myc; D005865:Gestational Age; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016274:Oncogene Protein p55(v-myc) / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology*; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D016274:Oncogene Protein p55(v-myc); D011994:Recombinant Proteins; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D003994:Bucladesine; D007608:Kainic Acid; D005998:Glycine