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Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons

Pereira, Maria LU ; Birtele, Marcella LU ; Shrigley, Shelby LU ; Benitez, Julio Aguila; Hedlund, Eva; Parmar, Malin LU and Ottosson, Daniella Rylander LU (2017) In Stem Cell Reports 9(3). p.742-751
Abstract

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... (More)

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. In this study, Parmar, Ottosson, and colleagues show how endogenous NG2 glia can be reprogrammed into GABAergic interneurons of different subtypes, the majority of them with properties of fast-spiking parvalbumin-containing interneurons. This neuronal subtype has been implicated in several neurological diseases, and the findings can open up new therapeutic options.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Environmental effect, Functional neurons, in vivo reprogramming, Interneurons, Midbrain, NG2-glia, Striatum
in
Stem Cell Reports
volume
9
issue
3
pages
742 - 751
publisher
Cell Press
external identifiers
  • scopus:85028056972
ISSN
2213-6711
DOI
10.1016/j.stemcr.2017.07.023
language
English
LU publication?
yes
id
5805be0e-9ca4-4365-bea9-7520eaa41796
date added to LUP
2017-09-14 14:30:11
date last changed
2017-09-15 03:00:03
@article{5805be0e-9ca4-4365-bea9-7520eaa41796,
  abstract     = {<p>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. In this study, Parmar, Ottosson, and colleagues show how endogenous NG2 glia can be reprogrammed into GABAergic interneurons of different subtypes, the majority of them with properties of fast-spiking parvalbumin-containing interneurons. This neuronal subtype has been implicated in several neurological diseases, and the findings can open up new therapeutic options.</p>},
  author       = {Pereira, Maria and Birtele, Marcella and Shrigley, Shelby and Benitez, Julio Aguila and Hedlund, Eva and Parmar, Malin and Ottosson, Daniella Rylander},
  issn         = {2213-6711},
  keyword      = {Environmental effect,Functional neurons,in vivo reprogramming,Interneurons,Midbrain,NG2-glia,Striatum},
  language     = {eng},
  number       = {3},
  pages        = {742--751},
  publisher    = {Cell Press},
  series       = {Stem Cell Reports},
  title        = {Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2017.07.023},
  volume       = {9},
  year         = {2017},
}