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Title: Efficient and Reproducible Myogenic Differentiation from Human iPS Cells: Prospects for Modeling Miyoshi Myopathy In Vitro
Authors: Tanaka, Akihito
Woltjen, Knut  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-2293-1183 (unconfirmed)
Miyake, Katsuya
Hotta, Akitsu  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-2619-7441 (unconfirmed)
Ikeya, Makoto  kyouindb  KAKEN_id
Yamamoto, Takuya  kyouindb  KAKEN_id
Nishino, Tokiko
Shoji, Emi
Sehara-Fujisawa, Atsuko
Manabe, Yasuko
Fujii, Nobuharu
Hanaoka, Kazunori
Era, Takumi
Yamashita, Satoshi
Isobe, Ken-ichi
Kimura, En
Sakurai, Hidetoshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-5383-9366 (unconfirmed)
Author's alias: 櫻井, 英俊
Issue Date: 23-Apr-2013
Publisher: Public Library of Science
Journal title: PLoS ONE
Volume: 8
Issue: 4
Thesis number: e61540
Abstract: The establishment of human induced pluripotent stem cells (hiPSCs) has enabled the production of in vitro, patient-specific cell models of human disease. In vitro recreation of disease pathology from patient-derived hiPSCs depends on efficient differentiation protocols producing relevant adult cell types. However, myogenic differentiation of hiPSCs has faced obstacles, namely, low efficiency and/or poor reproducibility. Here, we report the rapid, efficient, and reproducible differentiation of hiPSCs into mature myocytes. We demonstrated that inducible expression of myogenic differentiation1 (MYOD1) in immature hiPSCs for at least 5 days drives cells along the myogenic lineage, with efficiencies reaching 70–90%. Myogenic differentiation driven by MYOD1 occurred even in immature, almost completely undifferentiated hiPSCs, without mesodermal transition. Myocytes induced in this manner reach maturity within 2 weeks of differentiation as assessed by marker gene expression and functional properties, including in vitro and in vivo cell fusion and twitching in response to electrical stimulation. Miyoshi Myopathy (MM) is a congenital distal myopathy caused by defective muscle membrane repair due to mutations in DYSFERLIN. Using our induced differentiation technique, we successfully recreated the pathological condition of MM in vitro, demonstrating defective membrane repair in hiPSC-derived myotubes from an MM patient and phenotypic rescue by expression of full-length DYSFERLIN (DYSF). These findings not only facilitate the pathological investigation of MM, but could potentially be applied in modeling of other human muscular diseases by using patient-derived hiPSCs.
Description: 効率よく、再現性高くヒトiPS細胞から筋肉細胞を作製 -筋肉疾患の創薬プラットフォームの開発に向けて-. 京都大学プレスリリース. 2013-04-24.
Rights: © 2013 Tanaka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/2433/173620
DOI(Published Version): 10.1371/journal.pone.0061540
PubMed ID: 23626698
Related Link: https://www.kyoto-u.ac.jp/static/ja/news_data/h/h1/news6/2013/130424_1.htm
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