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  4. Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson's disease model
 
research article

Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson's disease model

Rivetti di Val Cervo, Pia
•
Romanov, Roman A
•
Spigolon, Giada
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April 10, 2017
Nature Biotechnology

Cell replacement therapies for neurodegenerative disease have focused on transplantation of the cell types affected by the pathological process. Here we describe an alternative strategy for Parkinson's disease in which dopamine neurons are generated by direct conversion of astrocytes. Using three transcription factors, NEUROD1, ASCL1 and LMX1A, and the microRNA miR218, collectively designated NeAL218, we reprogram human astrocytes in vitro, and mouse astrocytes in vivo, into induced dopamine neurons (iDANs). Reprogramming efficiency in vitro is improved by small molecules that promote chromatin remodeling and activate the TGFβ, Shh and Wnt signaling pathways. The reprogramming efficiency of human astrocytes reaches up to 16%, resulting in iDANs with appropriate midbrain markers and excitability. In a mouse model of Parkinson's disease, NeAL218 alone reprograms adult striatal astrocytes into iDANs that are excitable and correct some aspects of motor behavior in vivo, including gait impairments. With further optimization, this approach may enable clinical therapies for Parkinson's disease by delivery of genes rather than cells.

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Type
research article
DOI
10.1038/nbt.3835
Web of Science ID

WOS:000400809800019

Scopus ID

2-s2.0-85019089031

PubMed ID

28398344

Author(s)
Rivetti di Val Cervo, Pia
Romanov, Roman A
Spigolon, Giada
Masini, Débora
Martín-Montañez, Elisa
Toledo, Enrique M
La Manno, Gioele  
Feyder, Michael
Pifl, Christian
Ng, Yi-Han
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Date Issued

2017-04-10

Published in
Nature Biotechnology
Volume

35

Issue

5

Start page

444

End page

452

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
UPLAMANNO  
Available on Infoscience
May 1, 2019
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/156216
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