Activation of AMPK Promotes Maturation of Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells

作者全名："Ye, Liang; Zhang, Xinyuan; Zhou, Qin; Tan, Bin; Xu, Hao; Yi, Qin; Yan, Liang; Xie, Min; Zhang, Yin; Tian, Jie; Zhu, Jing"

作者地址："[Ye, Liang; Zhang, Xinyuan; Zhou, Qin; Tan, Bin; Yi, Qin; Yan, Liang; Xie, Min; Zhang, Yin; Zhu, Jing] Chongqing Med Univ, China Int Sci & Technol Cooperat Base Child Dev &, Childrens Hosp,Natl Clin Res Ctr Child Hlth & Dis, Dept Pediat Res Inst,Minist Educ,Key Lab Child De, Chongqing, Peoples R China; [Ye, Liang; Zhang, Xinyuan; Zhou, Qin; Tan, Bin; Xu, Hao; Yi, Qin; Yan, Liang; Xie, Min; Zhang, Yin; Tian, Jie; Zhu, Jing] Chongqing Key Lab Pediat, Chongqing, Peoples R China; [Tian, Jie] Chongqing Med Univ, China Int Sci & Technol Cooperat Base Child Dev &, Childrens Hosp,Natl Clin Res Ctr Child Hlth & Dis, Dept Cardiovasc Internal Med,Minist Educ,Key Lab, Chongqing, Peoples R China; [Xu, Hao] Chongqing Med Univ, China Int Sci & Technol Cooperat Base Child Dev &, Childrens Hosp,Natl Clin Res Ctr Child Hlth & Dis, Dept Clin Lab,Minist Educ,Key Lab Child Dev & Dis, Chongqing, Peoples R China"

通信作者："Zhu, J (corresponding author), Chongqing Med Univ, China Int Sci & Technol Cooperat Base Child Dev &, Childrens Hosp,Natl Clin Res Ctr Child Hlth & Dis, Dept Pediat Res Inst,Minist Educ,Key Lab Child De, Chongqing, Peoples R China.; Zhu, J (corresponding author), Chongqing Key Lab Pediat, Chongqing, Peoples R China."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000631429700001

JCR分区：Q1

影响因子：5.5

年份：2021

卷号：9

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：hiPSCs; hiPSC-CMs; AMPK; mitochondrial; cardiomyocyte maturation

摘要："Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) (hiPSC-CMs) are a promising cell source for disease modeling, myocardial regeneration, and drug assessment. However, hiPSC-CMs have certain immature fetal CM-like properties that are different from the characteristics of adult CMs in several aspects, including cellular structure, mitochondrial function, and metabolism, thus limiting their applications. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is an energy-sensing protein kinase involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in cardiomyocytes. This study investigated the effects of AMPK on the maturation of hiPSC-CMs. Activation of AMPK in hiPSC-CMs significantly increased the expression of CM-specific markers and resulted in a more mature myocardial structure compared to that in the control cells. We found that activation of AMPK improved mitochondrial oxidative phosphorylation (OxPhos) and the oxygen consumption rate (OCR). Additionally, our data demonstrated that activation of AMPK increased mitochondrial fusion to promote the maturation of mitochondrial structure and function. Overall, activation of AMPK is an effective approach to promote hiPSC-CMs maturation, which may enhance the utility of hiPSC-CMs in clinical applications."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81670270, 81700250]"

基金资助正文：The National Natural Science Foundation of China (Grant Nos. 81670270 and 81700250) supported this work.