PGC-1α promotes mitochondrial respiration and biogenesis during the differentiation of hiPSCs into cardiomyocytes

Qin Zhou; Hao Xu; Liang Yan; Liang Ye; Xinyuan Zhang; Bin Tan; Qin Yi; Jie Tian; Jing Zhu

doi:10.1016/j.gendis.2020.12.006

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PGC-1α promotes mitochondrial respiration and biogenesis during the differentiation of hiPSCs into cardiomyocytes

Full-length article | 更新时间：2022-06-24

- PGC-1α promotes mitochondrial respiration and biogenesis during the differentiation of hiPSCs into cardiomyocytes
- PGC-1α promotes mitochondrial respiration and biogenesis during the differentiation of hiPSCs into cardiomyocytes
- Genes & Diseases 2021年8卷第6期
- 作者机构：
  
  1. Department of Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders (Chongqing) China International Science and Technology Cooperation Base of Child Development and Critical Disorders Children’s Hospital of Chongqing Medical University,Chongqing,PR China,400000
  2. Chongqing Key Laboratory of Pediatrics,Chongqing,PR China,400000
  3. Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China,Sichuan Province,Chengdu,PR China,610073
  4. Department of Clinical Laboratory Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders (Chongqing) China International Science and Technology Cooperation Base of Child Development and Critical Disorders Children’s Hospital of Chongqing Medical University,Chongqing,PR China,400000
  5. Department of Cardiovascular (Internal Medicine), Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders (Chongqing) China International Science and Technology Cooperation Base of Child Development and Critical Disorders Children’s Hospital of Chongqing Medical University,Chongqing,PR China,400000
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2020.12.006
  中图分类号：
- 纸质出版日期：2021，
  
  网络出版日期：2021-11-1，
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Qin Zhou, Hao Xu, Liang Yan, 等. PGC-1α promotes mitochondrial respiration and biogenesis during the differentiation of hiPSCs into cardiomyocytes[J]. Genes & Diseases, 2021,8(6).

Qin Zhou, Hao Xu, Liang Yan, et al. PGC-1α promotes mitochondrial respiration and biogenesis during the differentiation of hiPSCs into cardiomyocytes[J]. Genes & Diseases, 2021,8(6).
Qin Zhou, Hao Xu, Liang Yan, 等. PGC-1α promotes mitochondrial respiration and biogenesis during the differentiation of hiPSCs into cardiomyocytes[J]. Genes & Diseases, 2021,8(6). DOI： 10.1016/j.gendis.2020.12.006.

Qin Zhou, Hao Xu, Liang Yan, et al. PGC-1α promotes mitochondrial respiration and biogenesis during the differentiation of hiPSCs into cardiomyocytes[J]. Genes & Diseases, 2021,8(6). DOI： 10.1016/j.gendis.2020.12.006.

摘要

Abstract

lthough it is widely accepted that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are readily available

robustly reproducible

and physiologically appropriate human cells for clinical applications and research in the cardiovascular field

hiPSC-CMs cultured

in vitro

retain an immature metabolic phenotype that limits their application

and little is known about the underlying molecular mechanism controlling mitochondrial metabolic maturation during human induced pluripotent stem cells (hiPSCs ) differentiation into cardiomyocytes. In this study

we found that peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) played an important role in inducing mitochondrial biogenesis and establishing oxidative phosphorylation (OXPHOS) during the cardiac differentiation of hiPSCs. Knocking down PGC-1α by siRNA impaired mitochondrial respiration

while upregulating PGC-1α by ZLN005 promoted mitochondrial biosynthesis and function by regulating the expression of downstream genes involved in mitochondrial dynamics and oxidative metabolism in hiPSC-CMs. Furthermore

we found that estrogen-related receptor α (ERRα) was required for the induction of PGC-1α stimulatory effects in hiPSC-CMs. These findings provide key insights into the molecular control of mitochondrial metabolism during cardiac differentiation and may be used to generate more metabolically mature cardiomyocytes for application.

关键词

Keywords

Cardiac differentiationhiPSCsMitochondrial metabolismPGC-1αMaturation

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