miR-34b/c regulates Wnt1 and enhances mesencephalic dopaminergic neuron differentiation

De Gregorio, Roberto, Pulcrano, Salvatore, De Sanctis, Claudia, Volpicelli, Floriana, Guatteo, Ezia, Von Oerthel, Lars, Esposito, Roberta, Piscitelli, Rosa Maria, Perrone Capano, Carla, Costa, Valerio, Greco, Dario, Smidt, Marten, Di Porzio, Umberto, Caiazzo, Massimiliano, Biagio Mercuri, Nicola, Li, Meng ORCID: https://orcid.org/0000-0002-4803-4643 and Bellenchi, Gian Carlo 2018. miR-34b/c regulates Wnt1 and enhances mesencephalic dopaminergic neuron differentiation. Stem Cell Reports 10 (4) , pp. 1237-1250. 10.1016/j.stemcr.2018.02.006

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Publisher:	Elsevier
ISSN:	2213-6711
Date of First Compliant Deposit:	2 February 2018
Date of Acceptance:	9 February 2018
Last Modified:	07 May 2023 13:34
URI:	https://orca.cardiff.ac.uk/id/eprint/108746

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