ERRγ enhances cardiac maturation with T-tubule formation in human iPSC-derived cardiomyocytes

• Miki, Kenji

  Center for iPS Cell Research and Application, Kyoto University; Takeda-CiRA Joint program (T-CiRA)

• Deguchi, Kohei

  Takeda-CiRA Joint program (T-CiRA); Regenerative Medicine Unit, Takeda Pharmaceutical Company Limited

• Nakanishi-Koakutsu, Misato

  Center for iPS Cell Research and Application, Kyoto University; Takeda-CiRA Joint program (T-CiRA)

• Lucena-Cacace, Antonio

  Center for iPS Cell Research and Application, Kyoto University

• Kondo, Shigeru

  Takeda-CiRA Joint program (T-CiRA); Regenerative Medicine Unit, Takeda Pharmaceutical Company Limited

• Fujiwara, Yuya

  Center for iPS Cell Research and Application, Kyoto University; Takeda-CiRA Joint program (T-CiRA)

• Hatani, Takeshi

  Center for iPS Cell Research and Application, Kyoto University; Takeda-CiRA Joint program (T-CiRA)

• Sasaki, Masako

  Center for iPS Cell Research and Application, Kyoto University; Takeda-CiRA Joint program (T-CiRA)

• Naka, Yuki

  Center for iPS Cell Research and Application, Kyoto University; Takeda-CiRA Joint program (T-CiRA)

• Okubo, Chikako

  Center for iPS Cell Research and Application, Kyoto University

• Narita, Megumi

  Center for iPS Cell Research and Application, Kyoto University

• Takei, Ikue

  Center for iPS Cell Research and Application, Kyoto University; Takeda-CiRA Joint program (T-CiRA)

• Napier, Stephanie C.

  Takeda-CiRA Joint program (T-CiRA); Regenerative Medicine Unit, Takeda Pharmaceutical Company Limited

• Sugo, Tsukasa

  GenAhead Bio Inc.

• Imaichi, Sachiko

  Pharmaceutical Science, Takeda Pharmaceutical Company Limited

• Monjo, Taku

  IBL, Takeda Pharmaceutical Company Limited

• Ando, Tatsuya

  IBL, Takeda Pharmaceutical Company Limited

• Tamura, Norihisa

  Takeda-CiRA Joint program (T-CiRA); Regenerative Medicine Unit, Takeda Pharmaceutical Company Limited

• Imahashi, Kenichi

  Takeda-CiRA Joint program (T-CiRA); Regenerative Medicine Unit, Takeda Pharmaceutical Company Limited

• Nishimoto, Tomoyuki

  Takeda-CiRA Joint program (T-CiRA); Regenerative Medicine Unit, Takeda Pharmaceutical Company Limited

• Yoshida, Yoshinori

  Center for iPS Cell Research and Application, Kyoto University; Takeda-CiRA Joint program (T-CiRA)

Abstract

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.

Lowering the cost of heart cell therapies. 京都大学プレスリリース. 2021-06-21.

Journal

• Nature Communications

  Nature Communications 12 3596-, 2021

  Springer Nature

Keywords

• Heart stem cells
• Pluripotent stem cells
• Screening
• Stem-cell differentiation

Details

• CRID: 1050570000411125248
• NII Article ID: 120007089250
• DOI: 10.1038/s41467-021-23816-3
• ISSN: 20411723
• HANDLE: 2433/263915
• Web Site: https://www.nature.com/articles/s41467-021-23816-3.pdf
• Web Site: https://www.nature.com/articles/s41467-021-23816-3
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN