Journal
STEM CELL REPORTS
Volume 9, Issue 3, Pages 742-751Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.07.023
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Funding
- European Research Council under the European Union [602278]
- ERC [30971]
- New York Stem Cell Foundation
- Swedish Research Council
- Swedish Parkinson Foundation
- Strategic Research Area at Lund University Multipark
- Parkinson Research Foundation
- Svenska sallskapet for medicinsk forskning, Fysiografen
- Ahlens-stiftelsen in Sweden
- BrainMatTrain
- European Union under the Marie Sklodowska-Curie Initial Training Network [H2020-MSCA-ITN-2015]
- [676408]
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Converting resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward toward the possibility of treating brain injuries or diseases. To date, it has been possible to obtain GABAergic and glutamatergic neurons via in vivo conversion, but the precise phenotype of these cells has not yet been analyzed in detail. Here, we show that neurons reprogrammed using Ascl1, Lmx1a, and Nurr1 functionally mature and integrate into existing brain circuitry and that the majority of the reprogrammed neurons have properties of fast-spiking, parvalbumin-containing interneurons. When testing different combinations of genes for neural conversion with a focus on pro-neural genes and dopamine fate determinants, we found that functional neurons can be generated using different gene combinations and in different brain regions and that most of the reprogrammed neurons become interneurons, independently of the combination of reprogramming factors used.
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