PMID- 33768096 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210327 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 9 DP - 2021 TI - Activation of AMPK Promotes Maturation of Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells. PG - 644667 LID - 10.3389/fcell.2021.644667 [doi] LID - 644667 AB - 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. CI - Copyright (c) 2021 Ye, Zhang, Zhou, Tan, Xu, Yi, Yan, Xie, Zhang, Tian and Zhu. FAU - Ye, Liang AU - Ye L AD - 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, China. AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. FAU - Zhang, Xinyuan AU - Zhang X AD - 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, China. AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. FAU - Zhou, Qin AU - Zhou Q AD - 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, China. AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. FAU - Tan, Bin AU - Tan B AD - 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, China. AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. FAU - Xu, Hao AU - Xu H AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. AD - 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, China. FAU - Yi, Qin AU - Yi Q AD - 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, China. AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. FAU - Yan, Liang AU - Yan L AD - 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, China. AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. FAU - Xie, Min AU - Xie M AD - 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, China. AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. FAU - Zhang, Yin AU - Zhang Y AD - 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, China. AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. FAU - Tian, Jie AU - Tian J AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. AD - 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, China. FAU - Zhu, Jing AU - Zhu J AD - 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, China. AD - Chongqing Key Laboratory of Pediatrics, Chongqing, China. LA - eng PT - Journal Article DEP - 20210309 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC7985185 OTO - NOTNLM OT - AMPK OT - cardiomyocyte maturation OT - hiPSC-CMs OT - hiPSCs OT - mitochondrial EDAT- 2021/03/27 06:00 MHDA- 2021/03/27 06:01 PMCR- 2021/01/01 CRDT- 2021/03/26 07:00 PHST- 2020/12/21 00:00 [received] PHST- 2021/02/18 00:00 [accepted] PHST- 2021/03/26 07:00 [entrez] PHST- 2021/03/27 06:00 [pubmed] PHST- 2021/03/27 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2021.644667 [doi] PST - epublish SO - Front Cell Dev Biol. 2021 Mar 9;9:644667. doi: 10.3389/fcell.2021.644667. eCollection 2021.