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

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De Gregorio , R , Pulcrano , S , De Sanctis , C , Volpicelli , F , Guatteo , E , von Oerthel , L , Latagliata , E C , Esposito , R , Piscitelli , R M , Perrone-Capano , C , Costa , V , Greco , D , Puglisi-Allegra , S , Smidt , M P , di Porzio , U , Caiazzo , M , Mercuri , N B , Li , M & Bellenchi , G C 2018 , ' miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation ' , Stem cell reports , vol. 10 , no. 4 , pp. 1237-1250 . https://doi.org/10.1016/j.stemcr.2018.02.006

Title: miR-34b/c Regulates Wnt1 and Enhances Mesencephalic Dopaminergic Neuron Differentiation
Author: De Gregorio, Roberto; Pulcrano, Salvatore; De Sanctis, Claudia; Volpicelli, Floriana; Guatteo, Ezia; von Oerthel, Lars; Latagliata, Emanuele Claudio; Esposito, Roberta; Piscitelli, Rosa Maria; Perrone-Capano, Carla; Costa, Valerio; Greco, Dario; Puglisi-Allegra, Stefano; Smidt, Marten P.; di Porzio, Umberto; Caiazzo, Massimiliano; Mercuri, Nicola Biagio; Li, Meng; Bellenchi, Gian Carlo
Contributor: University of Helsinki, Institute of Biotechnology
Date: 2018-04-10
Language: eng
Number of pages: 14
Belongs to series: Stem cell reports
ISSN: 2213-6711
URI: http://hdl.handle.net/10138/239260
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.
Subject: PLURIPOTENT STEM-CELLS
PARKINSONS-DISEASE
DIRECT CONVERSION
HUMAN FIBROBLASTS
SUBSTANTIA-NIGRA
STRIATAL NEURONS
PROGENITOR FATE
GENE-EXPRESSION
MIDBRAIN
NEUROGENESIS
1182 Biochemistry, cell and molecular biology
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