期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 31, 页码 12556-12561出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1209523109
关键词
neurons; reprogramming; stem cells
资金
- California Institute for Regenerative Medicine [RL1-00649-1, RC1-00115-1]
- Lookout Fund
- Mathers Foundation
- Helmsley Foundation
- JPB Medical Foundation
- Ministerio de Economia y Competitividad
- Fundacion Cellex
- Sanofi
- G. Harold and Leila Y. Mathers Charitable Foundation
- Leona M. and Harry B. Helmsley Charitable Trust
The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific sets of transcription 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 neuronal-like cells (CB-iNCs) by the ectopic expression of the transcription factor Sox2, a process that is further augmented by the combination of Sox2 and c-Myc. Gene-expression analysis, immunophenotyping, 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.
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