miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation.
Stem Cell Reports
; 10(4): 1237-1250, 2018 04 10.
Article
in En
| MEDLINE
| ID: mdl-29526736
ABSTRACT
The differentiation of dopaminergic neurons requires concerted action of morphogens and transcription factors acting in a precise and well-defined time window. Very little is known about the potential role of microRNA in these events. By performing a microRNA-mRNA paired microarray screening, we identified miR-34b/c among the most upregulated microRNAs during dopaminergic differentiation. Interestingly, miR-34b/c modulates Wnt1 expression, promotes cell cycle exit, and induces dopaminergic differentiation. When combined with transcription factors ASCL1 and NURR1, miR-34b/c doubled the yield of transdifferentiated fibroblasts into dopaminergic neurons. Induced dopaminergic (iDA) cells synthesize dopamine and show spontaneous electrical activity, reversibly blocked by tetrodotoxin, consistent with the electrophysiological properties featured by brain dopaminergic neurons. Our findings point to a role for miR-34b/c in neuronal commitment and highlight the potential of exploiting its synergy with key transcription factors in enhancing in vitro generation of dopaminergic neurons.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mesencephalon
/
Cell Differentiation
/
MicroRNAs
/
Wnt1 Protein
/
Dopaminergic Neurons
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Stem Cell Reports
Year:
2018
Document type:
Article
Affiliation country:
Italy