ERRγ Enhances Cardiac Maturation with T-tubule Formation in Human IPSC-derived Cardiomyocytes

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jun 22

PMID 34155205

Citations 35

Authors

Kenji Miki

Kohei Deguchi

Misato Nakanishi-Koakutsu

Antonio Lucena-Cacace

Shigeru Kondo

Yuya Fujiwara

Takeshi Hatani

Masako Sasaki

Yuki Naka

Chikako Okubo

Megumi Narita

Ikue Takei

Stephanie C Napier

Tsukasa Sugo

Sachiko Imaichi

Taku Monjo

Tatsuya Ando

Norihisa Tamura

Kenichi Imahashi

Tomoyuki Nishimoto

Yoshinori Yoshida

Affiliations

Soon will be listed here.

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 and TNNI3 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.

Citing Articles

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