ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2025
Promoting differentiation of human-induced pluripotent stem cells into sinoatrial node-like cells through programmed regulation of AMPK signalling pathway.
Article in Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2citing papers in PubMed
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1 · What the graph read from it
What it found
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5 · Who and what money
Authors and funding
12 authors.
Feng LiuDepartment of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.ORCID 0009-0009-8583-1287
Zongqian XueDepartment of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.
Huan LanKey Laboratory of Medical Electrophysiology of Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.ORCID 0000-0001-8027-448X
Juyi WanDepartment of Cardiovascular Surgery, the Affiliated Hospital, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of Cardiovascular Remodelling and Dysfunction, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Chenyu YangDepartment of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.
Lukas CyganekStem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0001-9120-1382
Nazha HamdaniInstitute of Physiology, Department of Cellular and Translational Physiology, Medical Faculty, Ruhr University Bochum, Bochum, Germany.ORCID 0000-0002-3053-0008
Fengxu YuDepartment of Cardiovascular Surgery, the Affiliated Hospital, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of Cardiovascular Remodelling and Dysfunction, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.ORCID 0000-0001-9907-6096
Bin LiaoDepartment of Cardiovascular Surgery, the Affiliated Hospital, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of Cardiovascular Remodelling and Dysfunction, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Xiaobo ZhouDepartment of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.ORCID 0000-0002-5895-0127
Ibrahim El-BattrawyInstitute of Physiology, Department of Cellular and Translational Physiology, Medical Faculty, Ruhr University Bochum, Bochum, Germany.ORCID 0000-0002-0139-1045
Ibrahim AkinDepartment of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.ORCID 0000-0003-1974-6147
Funding
Deutsche Forschungsgemeinschaft 7512/2-4Deutsche Forschungsgemeinschaft HA 7512/2-1DZHKElse Kröner Foundation 2022 EKES.48German Foundation of Heart Research 739593German Heart FoundationGerman Ministry of Education and Research 81Z0500204Hector Foundation M2401Institute of Cardiovascular ResearchKey Laboratory of Medical ElectrophysiologyLuzhou Science & Technology Office 2024WGR203Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan ProvinceNational Science Foundation of China 82070277National Science Foundation of China 82170325Science and Technology Strategic Cooperation Program of Luzhou Municipal People's Government and South Medical University 2024LZXNYDJ099Sichuan Science and Technology Program 2021YJ0207Sichuan Science and Technology Program 2022YFS0607Sichuan Science and Technology Program 2022YFS0610Sichuan Science and Technology Program 2025ZNFSC0708Southwest Medical University HR24077
6 · The paper itself
Abstract
aimsThe differentiation of human-induced pluripotent stem cells (hiPSCs) into sinoatrial node (SAN)-like cells (SANLCs) remains challenged by complex differentiation protocols and low efficiency. This study aims to reveal the role of AMPK signalling in the differentiation process of hiPSCs into SANLCs, providing new strategies for obtaining SANLCs in vitro. METHODS AND
resultsCells from the cardiac mesodermal stage, cardiac progenitor cell stage, and cardiomyocyte stage during differentiation of hiPSCs to cardiomyocytes (hiPSC-CMs) were taken for transcriptome sequencing and analyses. PCR, immunostaining, western blot, FACS, and patch-clamp techniques were employed for the analyses of differentiated hiPSC-CMs. Kyoto Encyclopedia of Genes and Genomes analysis identified that the AMPK signalling pathway is significantly enriched with the expression of NKX2.5 (sinus node cell development-related transcription factor). The early activation and late inhibition of AMPK signalling were both effective in the up-regulation of SANLC markers. In addition, the combined manipulation of both stages further enhanced the differentiation efficiency reflected by higher SANLC marker expression, which was also confirmed at the protein level by immunofluorescence, western blot, and flow cytometry analyses. SANLCs obtained from the differentiation with combined modulation of AMPK signalling displayed typical features of native pacemaker cells in the heart, including ion channel currents (IKAch, ICaT, ICaL, If), action potentials, and robust autonomic responsiveness to both β-adrenergic and muscarinic stimulation.
conclusionEarly activation and then inhibition of the AMPK signalling pathway during the differentiation process can promote hiPSC differentiation to SANLCs, which may provide a novel strategy for obtaining SANLCs for studies on SAN diseases.
Indexed as
AMP-Activated Protein KinasesCell DifferentiationInduced Pluripotent Stem CellsMyocytes, CardiacSinoatrial NodeAction PotentialsCells, CulturedHomeobox Protein Nkx-2.5HumansSignal TransductionAMP-Activated Protein KinasesHomeobox Protein Nkx-2.5NKX2-5 protein, humanAMPK signallingHuman-induced pluripotent stem cellsSinoatrial node-like cells
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.
Promoting differentiation of human-induced pluripotent stem cells into sinoatrial node-like cells through programmed regulation of AMPK signalling pathway. · full record | OpenQuestion