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タイトル: | ERRγ enhances cardiac maturation with T-tubule formation in human iPSC-derived cardiomyocytes |
著者: | Miki, Kenji Deguchi, Kohei Nakanishi-Koakutsu, Misato Lucena-Cacace, Antonio Kondo, Shigeru Fujiwara, Yuya Hatani, Takeshi Sasaki, Masako Naka, Yuki Okubo, Chikako Narita, Megumi Takei, Ikue Napier, Stephanie C. Sugo, Tsukasa Imaichi, Sachiko Monjo, Taku Ando, Tatsuya Tamura, Norihisa Imahashi, Kenichi Nishimoto, Tomoyuki Yoshida, Yoshinori https://orcid.org/0000-0001-5511-9090 (unconfirmed) |
著者名の別形: | 三木, 健嗣 出口, 康平 小圷, 美聡 藤原, 侑哉 羽渓, 健 佐々木, 成子 中, 侑希 大久保, 周子 成田, 恵 周郷, 司 西本, 誠之 吉田, 善紀 |
キーワード: | Heart stem cells Pluripotent stem cells Screening Stem-cell differentiation |
発行日: | 2021 |
出版者: | Springer Nature |
誌名: | Nature Communications |
巻: | 12 |
論文番号: | 3596 |
抄録: | One of the earliest maturation steps in cardiomyocytes (CMs) is the sarcomere protein isoform switch between TNNI1 and TNNI3 (fetal and neonatal/adult troponin I). Here, we generate human induced pluripotent stem cells (hiPSCs) carrying a TNNI1[EmGFP] and TNNI3[mCherry] double reporter to monitor and isolate mature sub-populations during cardiac differentiation. Extensive drug screening identifies two compounds, an estrogen-related receptor gamma (ERRγ) agonist and an S-phase kinase-associated protein 2 inhibitor, that enhances cardiac maturation and a significant change to TNNI3 expression. Expression, morphological, functional, and molecular analyses indicate that hiPSC-CMs treated with the ERRγ agonist show a larger cell size, longer sarcomere length, the presence of transverse tubules, and enhanced metabolic function and contractile and electrical properties. Here, we show that ERRγ-treated hiPSC-CMs have a mature cellular property consistent with neonatal CMs and are useful for disease modeling and regenerative medicine. |
記述: | ヒトのiPS細胞から新生児レベルまで成熟した心筋細胞を作製する. 京都大学プレスリリース. 2021-06-21. Lowering the cost of heart cell therapies. 京都大学プレスリリース. 2021-06-21. |
著作権等: | © The Author(s) 2021 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. |
URI: | http://hdl.handle.net/2433/263915 |
DOI(出版社版): | 10.1038/s41467-021-23816-3 |
PubMed ID: | 34155205 |
関連リンク: | https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/210621-180000.html https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/210621-180000.html |
出現コレクション: | 学術雑誌掲載論文等 |
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