Dual modulation of neuron-specific microRNAs and the REST complex promotes functional maturation of human adult induced neurons.

Autor: Birtele M; Department of Experimental Medical Science, Wallenberg Neuroscience Center, Division of Neurobiology, Lund Stem Cell Center, Lund University, Sweden., Sharma Y; Department of Experimental Medical Science, Wallenberg Neuroscience Center, Division of Neurobiology, Lund Stem Cell Center, Lund University, Sweden., Kidnapillai S; Regenerative Neurophysiology, BMC, Lund University, Sweden., Lau S; Department of Experimental Medical Science, Wallenberg Neuroscience Center, Division of Neurobiology, Lund Stem Cell Center, Lund University, Sweden., Stoker TB; Department of Experimental Medical Science, Wallenberg Neuroscience Center, Division of Neurobiology, Lund Stem Cell Center, Lund University, Sweden.; Department of Clinical Neuroscience and WT-MRC Cambridge Stem Cell Institute, University of Cambridge, UK., Barker RA; Department of Experimental Medical Science, Wallenberg Neuroscience Center, Division of Neurobiology, Lund Stem Cell Center, Lund University, Sweden.; Department of Clinical Neuroscience and WT-MRC Cambridge Stem Cell Institute, University of Cambridge, UK., Rylander Ottosson D; Department of Experimental Medical Science, Wallenberg Neuroscience Center, Division of Neurobiology, Lund Stem Cell Center, Lund University, Sweden.; Regenerative Neurophysiology, BMC, Lund University, Sweden., Drouin-Ouellet J; Faculté de Pharmacie, Université de Montréal, Canada., Parmar M; Department of Experimental Medical Science, Wallenberg Neuroscience Center, Division of Neurobiology, Lund Stem Cell Center, Lund University, Sweden.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2019 Dec; Vol. 593 (23), pp. 3370-3380. Date of Electronic Publication: 2019 Oct 10.
DOI: 10.1002/1873-3468.13612
Abstrakt: Direct neuronal reprogramming can be achieved using different approaches: by expressing neuronal transcription factors or microRNAs; and by knocking down neuronal repressive elements. However, there still exists a high variability in terms of the quality and maturity of the induced neurons obtained, depending on the reprogramming strategy employed. Here, we evaluate different long-term culture conditions and study the effect of expressing the neuronal-specific microRNAs, miR124 and miR9/9*, while reprogramming with forced expression of the transcription factors Ascl1, Brn2, and knockdown of the neuronal repressor REST. We show that the addition of microRNAs supports neuronal maturation in terms of gene and protein expression, as well as in terms of electrophysiological properties.
(© 2019 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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