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miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation

Roberto De Gregorio1, Salvatore Pulcrano2, Claudia De Sanctis3

  • 1Institute of Genetics and Biophysics, "Adriano Buzzati Traverso", CNR, 80131 Naples, Italy.

Stem Cell Reports
|March 13, 2018
PubMed

Insights

MicroRNA miR-34b/c significantly enhances dopaminergic neuron generation. This microRNA, when combined with transcription factors, doubles the yield of induced dopaminergic (iDA) cells from fibroblasts, offering a promising method for in vitro neurogenesis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Dopaminergic neuron differentiation involves complex interactions of morphogens and transcription factors.
  • The role of microRNAs in dopaminergic differentiation remains largely unexplored.

Purpose of the Study:

  • To investigate the role of microRNAs in dopaminergic neuron differentiation.
  • To identify specific microRNAs that can enhance the generation of dopaminergic neurons.

Main Methods:

  • MicroRNA-mRNA paired microarray screening was performed to identify differentially expressed microRNAs during dopaminergic differentiation.
  • The function of identified microRNAs was assessed in promoting dopaminergic differentiation, including their effect on cell cycle exit and Wnt1 expression.
  • Synergistic effects of microRNA-34b/c with transcription factors ASCL1 and NURR1 were evaluated in transdifferentiating fibroblasts into dopaminergic neurons.

Main Results:

  • miR-34b/c was identified as a significantly upregulated microRNA during dopaminergic differentiation.
  • miR-34b/c was shown to modulate Wnt1 expression, promote cell cycle exit, and induce dopaminergic differentiation.
  • Combining miR-34b/c with ASCL1 and NURR1 transcription factors doubled the yield of induced dopaminergic (iDA) cells from fibroblasts.
  • Generated iDA cells exhibited dopamine synthesis and electrophysiological properties characteristic of brain dopaminergic neurons.

Conclusions:

  • miR-34b/c plays a crucial role in neuronal commitment during dopaminergic differentiation.
  • The synergy between miR-34b/c and key transcription factors offers a potent strategy for enhancing in vitro generation of dopaminergic neurons.
Keywords:
Wnt pathwayWnt1dopamineepiSCmESCmiR34b/cmicroRNAreprogrammingtransdifferentiation

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