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

Birtele, Marcella LU orcid ; Sharma, Yogita LU ; Kidnapillai, Srisaiyini LU ; Lau, Shong LU ; Stoker, Thomas B. ; Barker, Roger A. LU ; Rylander Ottosson, Daniella LU ; Drouin-Ouellet, Janelle LU and Parmar, Malin LU orcid (2019) In FEBS Letters 593(23). p.3370-3380
Abstract

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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
direct reprogramming, electrophysiology, human adult neurons, induced neurons, miR124, miR9
in
FEBS Letters
volume
593
issue
23
pages
11 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85074443776
  • pmid:31535361
ISSN
0014-5793
DOI
10.1002/1873-3468.13612
language
English
LU publication?
yes
id
ac8505d5-aa1e-48f1-8dec-abe86fa9a4dc
date added to LUP
2019-11-22 12:36:42
date last changed
2024-04-16 23:51:06
@article{ac8505d5-aa1e-48f1-8dec-abe86fa9a4dc,
  abstract     = {{<p>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.</p>}},
  author       = {{Birtele, Marcella and Sharma, Yogita and Kidnapillai, Srisaiyini and Lau, Shong and Stoker, Thomas B. and Barker, Roger A. and Rylander Ottosson, Daniella and Drouin-Ouellet, Janelle and Parmar, Malin}},
  issn         = {{0014-5793}},
  keywords     = {{direct reprogramming; electrophysiology; human adult neurons; induced neurons; miR124; miR9}},
  language     = {{eng}},
  number       = {{23}},
  pages        = {{3370--3380}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{FEBS Letters}},
  title        = {{Dual modulation of neuron-specific microRNAs and the REST complex promotes functional maturation of human adult induced neurons}},
  url          = {{http://dx.doi.org/10.1002/1873-3468.13612}},
  doi          = {{10.1002/1873-3468.13612}},
  volume       = {{593}},
  year         = {{2019}},
}