{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Smith JGW"],"funding":["German Research Foundation","National Centre for the Replacement, Refinement and Reduction of Animals in Research","British Heart Foundation","Britain Israel Research and Academic Exchange Partnership","Una forma de hacer Europa","FEDER","German Ministry of Education and Research","Freie und Hansestadt Hamburg","European Commission","German Centre for Cardiovascular Research","Engineering and Physical Sciences Research Council","Centro de Investigación Biomédica en Red","European Research Council","Instituto de Salud Carlos III","Medical Research Council","Unión Europea","National Centre for the Replacement, Refinement &amp; Reduction of Animals"],"pagination":["1226-1243"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6235010"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(5)"],"pubmed_abstract":["Hypertrophic cardiomyopathy (HCM) is a primary disorder of contractility in heart muscle. To gain mechanistic insight and guide pharmacological rescue, this study models HCM using isogenic pairs of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the E99K-ACTC1 cardiac actin mutation. In both 3D engineered heart tissues and 2D monolayers, arrhythmogenesis was evident in all E99K-ACTC1 hiPSC-CMs. Aberrant phenotypes were most common in hiPSC-CMs produced from the heterozygote father. Unexpectedly, pathological phenotypes were less evident in E99K-expressing hiPSC-CMs from the two sons. Mechanistic insight from Ca<sup>2+</sup> handling expression studies prompted pharmacological rescue experiments, wherein dual dantroline/ranolazine treatment was most effective"],"journal":["Stem cell reports"],"pubmed_title":["Isogenic Pairs of hiPSC-CMs with Hypertrophic Cardiomyopathy/LVNC-Associated ACTC1 E99K Mutation Unveil Differential Functional Deficits."],"pmcid":["PMC6235010"],"funding_grant_id":["G113/30","PG/14/59/31000","RM/13/30157","NC/C013202/1","SP/15/9/31605","CB16/11/00425 617","1379951","DFG-Es-88/12-1, HA3423/5-1","MR/M017354/1","P47352/CRM","04BX14CDLG","FS/16/17/31663","NC/C013105/1","G0801098","CRACK-IT:35911-259146","RG/11/20/29266","RG/14/1/30588","MR/L012618/1","RG/15/6/31436","NC/K000225/1"],"pubmed_authors":["Eschenhagen T","Patel A","Hansen A","Scott E","Smith JGW","Denning C","Owen T","Harding SE","Marston S","Barriales-Villa R","Mannhardt I","Bhagwan JR","Mosqueira D","Monserrat L"],"additional_accession":[]},"is_claimable":false,"name":"Isogenic Pairs of hiPSC-CMs with Hypertrophic Cardiomyopathy/LVNC-Associated ACTC1 E99K Mutation Unveil Differential Functional Deficits.","description":"Hypertrophic cardiomyopathy (HCM) is a primary disorder of contractility in heart muscle. To gain mechanistic insight and guide pharmacological rescue, this study models HCM using isogenic pairs of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the E99K-ACTC1 cardiac actin mutation. In both 3D engineered heart tissues and 2D monolayers, arrhythmogenesis was evident in all E99K-ACTC1 hiPSC-CMs. Aberrant phenotypes were most common in hiPSC-CMs produced from the heterozygote father. Unexpectedly, pathological phenotypes were less evident in E99K-expressing hiPSC-CMs from the two sons. Mechanistic insight from Ca<sup>2+</sup> handling expression studies prompted pharmacological rescue experiments, wherein dual dantroline/ranolazine treatment was most effective","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Nov","modification":"2026-05-06T02:33:30.349Z","creation":"2019-03-27T00:08:27Z"},"accession":"S-EPMC6235010","cross_references":{"pubmed":["30392975"],"doi":["10.1016/j.stemcr.2018.10.006"]}}