{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["43(9)"],"submitter":["Givens SE"],"pubmed_abstract":["Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable cell type for studying human cardiac health and disease in vitro. However, it is not known whether hiPSC-CMs display sex dimorphism and therefore whether sex should be incorporated as a biological variable in in vitro studies that include this cell type. To date, the vast majority of studies that utilize hiPSC-CMs do not include both male and female sex nor stratify results based on sex because it is challenging to amass such a cohort of cells. Here, we generated 3 female and 3 male hiPSC lines from adult left ventricular cardiac fibroblasts as a resource for studying sex differences in in vitro cardiac models. We used this resource to generate hiPSC-CMs and maintained them in basal media without exogenous hormones. Functional assessment of CMs showed enhanced calcium handling in female-derived hiPSC-CMs relative to male. Bulk RNA sequencing revealed over 300 differentially expressed genes (DEGs) between male and female hiPSC-CMs. Gene ontology analysis of DEGs showed distinct differences in pathways related to cardiac pathology including cell-cell adhesion, metabolic processes, and response to ischemic stress. Differential expression of the sodium channel auxiliary unit SCN3B was found and validated through patch-clamp measurements of sodium currents, showing increased peak amplitude and window current in female hiPSC-CMs. These findings highlight the importance of considering sex as a variable when conducting studies to evaluate aspects of human cardiac health and disease related to CM function."],"journal":["Stem cells (Dayton, Ohio)"],"pagination":["sxaf038"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12371235"],"repository":["biostudies-literature"],"pubmed_title":["Healthy human induced pluripotent stem cell-derived cardiomyocytes exhibit sex dimorphism even without the addition of hormones."],"pmcid":["PMC12371235"],"pubmed_authors":["Dutton JR","Andebrhan AA","Ebrahimi-Barough S","Abrahante JE","Ogle BM","Schmuck EG","Xie A","Stanis N","Givens SE","Renaud A","Dudley S"],"additional_accession":[]},"is_claimable":false,"name":"Healthy human induced pluripotent stem cell-derived cardiomyocytes exhibit sex dimorphism even without the addition of hormones.","description":"Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable cell type for studying human cardiac health and disease in vitro. However, it is not known whether hiPSC-CMs display sex dimorphism and therefore whether sex should be incorporated as a biological variable in in vitro studies that include this cell type. To date, the vast majority of studies that utilize hiPSC-CMs do not include both male and female sex nor stratify results based on sex because it is challenging to amass such a cohort of cells. Here, we generated 3 female and 3 male hiPSC lines from adult left ventricular cardiac fibroblasts as a resource for studying sex differences in in vitro cardiac models. We used this resource to generate hiPSC-CMs and maintained them in basal media without exogenous hormones. Functional assessment of CMs showed enhanced calcium handling in female-derived hiPSC-CMs relative to male. Bulk RNA sequencing revealed over 300 differentially expressed genes (DEGs) between male and female hiPSC-CMs. Gene ontology analysis of DEGs showed distinct differences in pathways related to cardiac pathology including cell-cell adhesion, metabolic processes, and response to ischemic stress. Differential expression of the sodium channel auxiliary unit SCN3B was found and validated through patch-clamp measurements of sodium currents, showing increased peak amplitude and window current in female hiPSC-CMs. These findings highlight the importance of considering sex as a variable when conducting studies to evaluate aspects of human cardiac health and disease related to CM function.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-09T10:40:55.373Z","creation":"2026-04-08T00:48:29.014Z"},"accession":"S-EPMC12371235","cross_references":{"pubmed":["40578843"],"doi":["10.1093/stmcls/sxaf038"]}}