title: Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation "Memories".
abstract: The directed differentiation of human cardiomyocytes (CMs) from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation "memories" persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors.
authors.affiliation: Department of Diabetes Complications and Metabolism, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Tompkins
authors.affiliation: Department of Diabetes Complications and Metabolism, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Jung
authors.affiliation: Center for Biomedicine and Genetics, Duarte, CA 91010, USA; Sylvia R. and Isador A. Deutch Center for Applied Technology Development, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Center for Biomedicine and Genetics, Duarte, CA 91010, USA; Sylvia R. and Isador A. Deutch Center for Applied Technology Development, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Ziguang
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Center for Biomedicine and Genetics, Duarte, CA 91010, USA; Sylvia R. and Isador A. Deutch Center for Applied Technology Development, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Diabetes Complications and Metabolism, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Swetha
authors.initials: S
authors.lastname: Godatha
authors.affiliation: Department of Diabetes Complications and Metabolism, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lizhar
authors.affiliation: Biomedical Informatics Core, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Center for Biomedicine and Genetics, Duarte, CA 91010, USA; Sylvia R. and Isador A. Deutch Center for Applied Technology Development, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hsu
authors.affiliation: Center for Biomedicine and Genetics, Duarte, CA 91010, USA; Sylvia R. and Isador A. Deutch Center for Applied Technology Development, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Couture
authors.affiliation: Department of Diabetes Complications and Metabolism, Duarte, CA 91010, USA; Beckman Research Institute at City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Riggs
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005091:Exons; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome
keywords: Cardiomyocytes; Cardiomyogenesis; DNA methylation; Differentiation; Epigenetic; Good manufacturing practice, GMP, epigenetic memory, WNT, hedgehog, transforming growth factor, ROR2, PDGFRα, demethylation, TET, TDG, HOX, TBOX; Human embryonic stem cells; Long non-coding RNA; Mesoderm; Methylome; Pluripotent; Transcriptome; lncRNA