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Title: Simple Derivation of Spinal Motor Neurons from ESCs/iPSCs Using Sendai Virus Vectors
Authors: Goto, Kazuya  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-2235-3811 (unconfirmed)
Imamura, Keiko
Komatsu, Kenichi
Mitani, Kohnosuke
Aiba, Kazuhiro
Nakatsuji, Norio
Inoue, Makoto
Kawata, Akihiro
Yamashita, Hirofumi
Takahashi, Ryosuke  kyouindb  KAKEN_id
Inoue, Haruhisa  kyouindb  KAKEN_id
Author's alias: 後藤, 和也
今村, 恵子
小松, 研一
井上, 治久
Keywords: motor neurons
Sendai virus
induced pluripotent stem cells
embryonic stem cells
iPSC
ESC
differentiation
direct conversion
transcription factor
Issue Date: 17-Mar-2017
Publisher: Elsevier B.V.
Journal title: Molecular Therapy - Methods & Clinical Development
Volume: 4
Start page: 115
End page: 125
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons (MNs). Embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) now help us to understand the pathomechanisms of ALS via disease modeling. Various methods to differentiate ESCs/iPSCs into MNs by the addition of signaling molecules have been reported. However, classical methods require multiple steps, and newer simple methods using the transduction of transcription factors run the risk of genomic integration of the vector genes. Heterogeneity of the expression levels of the transcription factors also remains an issue. Here we describe a novel approach for differentiating human and mouse ESCs/iPSCs into MNs using a single Sendai virus vector encoding three transcription factors, LIM/homeobox protein 3, neurogenin 2, and islet-1, which are integration free. This single-vector method, generating HB9-positive cells on day 2 from human iPSCs, increases the ratio of MNs to neurons compared to the use of three separate Sendai virus vectors. In addition, the MNs derived via this method from iPSCs of ALS patients and model mice display disease phenotypes. This simple approach significantly reduces the efforts required to generate MNs, and it provides a useful tool for disease modeling.
Description: センダイウイルスベクターを用いてES細胞/iPS細胞から脊髄運動ニューロンを簡便に作製する技術開発. 京都大学プレスリリース. 2017-02-07.
Rights: © 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/2433/217986
DOI(Published Version): 10.1016/j.omtm.2016.12.007
Related Link: http://www.kyoto-u.ac.jp/ja/research/research_results/2016/170202_2.html
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