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Myocyte-specific enhancer factor 2c triggers transdifferentiation of adipose tissue-derived stromal cells into spontaneously beating cardiomyocyte-like cells
https://doi.org/10.24517/00060495
https://doi.org/10.24517/00060495910d53f9-e851-4cfc-a082-14cd45d83bc6
名前 / ファイル | ライセンス | アクション |
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ME-PR-TAKASHIMA-S-80848-3.pdf (11.8 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-02-18 | |||||
タイトル | ||||||
タイトル | Myocyte-specific enhancer factor 2c triggers transdifferentiation of adipose tissue-derived stromal cells into spontaneously beating cardiomyocyte-like cells | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
ID登録 | ||||||
ID登録 | 10.24517/00060495 | |||||
ID登録タイプ | JaLC | |||||
著者 |
Takashima, Shinichiro
× Takashima, Shinichiro× Usui, Soichiro× Inoue, Oto× Goten, Chiaki× Yamaguchi, Kosei× Takeda, Yusuke× Cui, Shihe× Sakai, Yoshio× Hayashi, Kenshi× Sakata, Kenji× Kawashiri, Masa-aki× Takamura, Masayuki |
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著者別表示 |
高島, 伸一郎
× 高島, 伸一郎× 薄井, 荘一郎× 井上, 己音× 林, 研至× 川尻, 剛照× 高村, 雅之 |
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書誌情報 |
Scientific Reports 巻 11, p. 1520, 発行日 2021-01-15 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2045-2322 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/s41598-020-80848-3 | |||||
出版者 | ||||||
出版者 | Nature Research | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Cardiomyocyte regeneration is limited in adults. The adipose tissue-derived stromal vascular fraction (Ad-SVF) contains pluripotent stem cells that rarely transdifferentiate into spontaneously beating cardiomyocyte-like cells (beating CMs). However, the characteristics of beating CMs and the factors that regulate the differentiation of Ad-SVF toward the cardiac lineage are unknown. We developed a simple culture protocol under which the adult murine inguinal Ad-SVF reproducibly transdifferentiates into beating CMs without induction. The beating CMs showed the striated ventricular phenotype of cardiomyocytes and synchronised oscillation of the intracellular calcium concentration among cells on day 28 of Ad-SVF primary culture. We also identified beating CM-fated progenitors (CFPs) and performed single-cell transcriptome analysis of these CFPs. Among 491 transcription factors that were differentially expressed (≥ 1.75-fold) in CFPs and the beating CMs, myocyte-specific enhancer 2c (Mef2c) was key. Transduction of Ad-SVF cells with Mef2c using a lentiviral vector yielded CFPs and beating CMs with ~ tenfold higher cardiac troponin T expression, which was abolished by silencing of Mef2c. Thus, we identified the master gene required for transdifferentiation of Ad-SVF into beating CMs. These findings will facilitate the development of novel cardiac regeneration therapies based on gene-modified, cardiac lineage-directed Ad-SVF cells. | |||||
権利 | ||||||
権利情報 | Copyright © 2021 The Author(s) 2020. Published by 2021 Springer Nature. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://www.nature.com/articles/s41598-020-80848-3 | |||||
関連名称 | https://www.nature.com/articles/s41598-020-80848-3 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://www.nature.com/srep/index.html | |||||
関連名称 | http://www.nature.com/srep/index.html |