SOX2 reprograms resident astrocytes into neural progenitors in the adult brain.
Stem Cell Reports
; 4(5): 780-94, 2015 May 12.
Article
em En
| MEDLINE
| ID: mdl-25921813
Glial cells can be in vivo reprogrammed into functional neurons in the adult CNS; however, the process by which this reprogramming occurs is unclear. Here, we show that a distinct cellular sequence is involved in SOX2-driven in situ conversion of adult astrocytes to neurons. This includes ASCL1(+) neural progenitors and DCX(+) adult neuroblasts (iANBs) as intermediates. Importantly, ASCL1 is required, but not sufficient, for the robust generation of iANBs in the adult striatum. These progenitor-derived iANBs predominantly give rise to calretinin(+) interneurons when supplied with neurotrophic factors or the small-molecule valproic acid. Patch-clamp recordings from the induced neurons reveal subtype heterogeneity, though all are functionally mature, fire repetitive action potentials, and receive synaptic inputs. Together, these results show that SOX2-mediated in vivo reprogramming of astrocytes to neurons passes through proliferative intermediate progenitors, which may be exploited for regenerative medicine.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Astrócitos
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Reprogramação Celular
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Fatores de Transcrição SOXB1
Limite:
Animals
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos