{"doi":"10.1016/j.stemcr.2020.06.012","title":"Sustained Activation of AMPK Enhances Differentiation of Human iPSC-Derived Cardiomyocytes via Sirtuin Activation","abstract":"Recent studies suggest that metabolic regulation may improve differentiation of cardiomyocytes derived from induced pluripotent stem cells (iPSCs). AMP-activated protein kinase (AMPK) is a master regulator of metabolic activities. We investigated whether AMPK participates in iPSC-derived cardiomyocyte differentiation. We observed that AMPK phosphorylation at Thr172 increased at day 9 but then decreased after day 11 of differentiation to cardiomyocytes. Inhibition of AMPK with compound C significantly reduced mRNA and protein expression of cardiac troponins TNNT2 and TNNI3. Moreover, sustained AMPK activation using AICAR from days 9 to 14 of differentiation increased mRNA and protein expression of both TNNT2 and TNNI3. AICAR decreased acetylation of histone 3 at Lys9 and 56 and histone 4 at Lys16 (known target sites for nuclear-localized sirtuins [SIRT1, SIRT6]), suggesting that AMPK activation enhances sirtuin activity. Sustained AMPK activation during days 9-14 of differentiation induces sirtuin-mediated histone deacetylation and may enhance cardiomyocyte differentiation from iPSCs.","journal":"Stem Cell Reports","year":2020,"id":100813,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":494216,"name":"Jessica C. Garbern","orcid":"0000-0002-2397-5180","position":1,"is_corresponding":false},{"id":3622,"name":"Sai Ma","orcid":"0000-0002-9785-7929","position":2,"is_corresponding":false},{"id":494217,"name":"Rebecca Sereda","orcid":"0000-0002-6168-3226","position":3,"is_corresponding":false},{"id":494938,"name":"Jeffrey Conde","orcid":null,"position":4,"is_corresponding":false},{"id":494939,"name":"Guido Krähenbühl","orcid":null,"position":5,"is_corresponding":false},{"id":494218,"name":"Gabriela O. Escalante","orcid":"0000-0002-0085-7966","position":6,"is_corresponding":false},{"id":494940,"name":"Aishah Ahmed","orcid":null,"position":7,"is_corresponding":false},{"id":3630,"name":"Jason D. Buenrostro","orcid":"0000-0001-9958-3987","position":8,"is_corresponding":false},{"id":294915,"name":"Richard Lee","orcid":"0000-0003-4687-1381","position":9,"is_corresponding":false},{"id":494937,"name":"Mohsen Sarikhani","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T22:39:01.863288Z","pmid":"32649901","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}