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Dual modulation of neuron‐specific microRNAs and the REST complex promotes functional maturation of human adult induced neurons
Author(s) -
Birtele Marcella,
Sharma Yogita,
Kidnapillai Srisaiyini,
Lau Shong,
Stoker Thomas B.,
Barker Roger A.,
Rylander Ottosson Daniella,
DrouinOuellet Janelle,
Parmar Malin
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13612
Subject(s) - reprogramming , gene knockdown , microrna , repressor , transcription factor , biology , microbiology and biotechnology , premovement neuronal activity , transcription (linguistics) , neuron , gene expression , neuroscience , gene , genetics , linguistics , philosophy
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.