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

Stem Cell Reports. 2018 Apr 10;10(4):1237-1250. doi: 10.1016/j.stemcr.2018.02.006. Epub 2018 Mar 8.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation*
  • Cell Transdifferentiation
  • Dopaminergic Neurons / cytology*
  • Dopaminergic Neurons / metabolism
  • Fibroblasts / cytology
  • Gene Expression Regulation
  • Germ Layers / cytology
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / metabolism
  • Mesencephalon / cytology*
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurogenesis / genetics
  • Transcription Factors / metabolism
  • Wnt Signaling Pathway
  • Wnt1 Protein / metabolism*


  • Homeodomain Proteins
  • MIRN34a microRNA, mouse
  • MicroRNAs
  • Transcription Factors
  • Wnt1 Protein
  • homeobox protein PITX3
  • Green Fluorescent Proteins