Identification of Nucleoside Analogs as Inducers of Neuronal Differentiation in a Human Reporter Cell Line and Adult Stem Cells

摘要: Nucleoside analogs (NSAs) were among the first chemotherapeutic agents and could also be useful for manipulation of cell fate. To investigate potential NSAs induction neuronal differentiation, we developed a novel phenotypic assay based on human neuron-committed teratocarcinoma line (NT2) as a model progenitors constructed NT2-based reporter that expressed eGFP under control neuron-specific promoter. We tested 38 structurally related determined their activity to induce differentiation by immunocytochemistry marker proteins, live imaging, fluorometric detection immunoblot analysis. identified twelve NSAs, which induced different extents. with highest carried halogen substituent at pyrimidine nucleobase an unmodified or 2'-O-methyl substituted 2-deoxy-β-D-ribofuranosyl residue glyconic moiety. Cladribine, purine nucleoside similar structural features in use treat leukemia multiple sclerosis, adult neural crest-derived stem cells. Our results suggest fate replacement therapy treatment neurodegenerative disorders. The data structure function relationship will help design compounds increased low toxicity.