Cord blood-derived neuronal cells by ectopic expression of SOX2 and c-MYC

The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific sets of transcrip- tion factors paves the way to novel therapeutic applications. Here we show that human cord blood (CB) CD133+ cells lose their hematopoietic signature and are c...

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Hauptverfasser: Giorgetti, Alessandra, Marchetto, Maria C.N, Li, Mo, Yu, Diana, Fazzina, Raffaella, Mu, Yangling, Adamo, Antonio, Paramonov, Ida, Castaño, Julio, Barragan Monasterio, Montserrat, Bardy, Cedric, Cassiani-Ingoni, Riccardo, Liu, Guang-Hui, Gage, Fred H, Izpisúa Belmonte, Juan Carlos
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Sprache:eng
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Zusammenfassung:The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific sets of transcrip- tion factors paves the way to novel therapeutic applications. Here we show that human cord blood (CB) CD133+ cells lose their hematopoietic signature and are converted into CB-induced neu- ronal-like cells (CB-iNCs) by the ectopic expression of the transcrip- tion factor Sox2, a process that is further augmented by the combination of Sox2 and c-Myc. Gene-expression analysis, immu- nophenotyping, and electrophysiological analysis show that CB- iNCs acquire a distinct neuronal phenotype characterized by the expression of multiple neuronal markers. CB-iNCs show the ability to fire action potentials after in vitro maturation as well as after in vivo transplantation into the mouse hippocampus. This system highlights the potential of CB cells and offers an alternative means to the study of cellular plasticity, possibly in the context of drug screening research and of future cell-replacement therapies.
ISSN:0027-8424
DOI:10.1073/pnas.1209523109