Stem Cell Reports
Volume 10, Issue 4, 10 April 2018, Pages 1237-1250
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Article
miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation

https://doi.org/10.1016/j.stemcr.2018.02.006Get rights and content
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Highlights

  • miR-34b/c is enriched in Pitx3-GFP+ mDA neurons

  • miR-34b/c targets Wnt1-3′ UTR

  • miR-34b/c is expressed during dopaminergic differentiation of mESCs

  • miR-34b/c enhances fibroblast transdifferentiation into functional iDA neurons

Summary

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.

Keywords

microRNA
dopamine
mESC
miR34b/c
epiSC
transdifferentiation
Wnt1
Wnt pathway
reprogramming

Cited by (0)

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Present address: Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, NY 10461, USA

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Co-first author