Journal
CELL STEM CELL
Volume 11, Issue 4, Pages 471-476Publisher
CELL PRESS
DOI: 10.1016/j.stem.2012.07.007
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [SPP1356]
- BMBF
- Bavarian State Ministry of Sciences, Research and the Arts
- binational SYSTHER-INREMOS Virtual Institute (German and Slovenian Federal Ministries of Education and Research)
- DFG [SFB 824]
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Reprogramming of somatic cells into neurons provides a new approach toward cell-based therapy of neurodegenerative diseases. A major challenge for the translation of neuronal reprogramming into therapy is whether the adult human brain contains cell populations amenable to direct somatic cell conversion. Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1. These induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrating into neural networks. Genetic fate-mapping in mice expressing an inducible Cre recombinase under the tissue-nonspecific alkaline phosphatase promoter corroborated the pericytic origin of the reprogrammed cells. Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates.
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