Phenotypic Reprogramming of Striatal Neurons into Dopaminergic Neuron-like Cells in the Adult Mouse Brain.
Stem Cell Reports
; 11(5): 1156-1170, 2018 11 13.
Article
em En
| MEDLINE
| ID: mdl-30318292
ABSTRACT
Neuronal subtype is largely fixed in the adult mammalian brain. Here, however, we unexpectedly reveal that adult mouse striatal neurons can be reprogrammed into dopaminergic neuron-like cells (iDALs). This in vivo phenotypic reprogramming can be promoted by a stem cell factor (SOX2), three dopaminergic neuron-enriched transcription regulators (NURR1, LMX1A, and FOXA2), and a chemical compound (valproic acid). Although the site of action of the reprogramming factors remains to be determined, immunohistochemistry and genetic lineage mappings confirm striatal neurons as the cell origin for iDALs. iDALs exhibit electrophysiological properties stereotypical to endogenous dopaminergic rather than striatal neurons. Together, these results indicate that neuronal phenotype can be reengineered even in the adult brain, implicating a therapeutic strategy for neurological diseases.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Corpo Estriado
/
Reprogramação Celular
/
Neurônios Dopaminérgicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos