title: Transcriptional Landscape of Cardiomyocyte Maturation.
abstract: Decades of progress in developmental cardiology has advanced our understanding of the early aspects of heart development, including cardiomyocyte (CM) differentiation. However, control of the CM maturation that is subsequently required to generate adult myocytes remains elusive. Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and identified a large number of genes whose expression shifts gradually and continuously during maturation. We generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs), which show discrete sets of key transcriptional regulators and pathways activated or suppressed during CM maturation. We developed a GRN-based program named MatStat(CM) that indexes CM maturation status. MatStat(CM) reveals that pluripotent-stem-cell-derived CMs mature early in culture but are arrested at the late embryonic stage with aberrant regulation of key transcription factors. Our study provides a foundation for understanding CM maturation.
authors.affiliation: Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Johns Hopkins Institute for Cell Engineering, Baltimore, MD 21205, USA.
authors.forename: Hideki
authors.initials: H
authors.lastname: Uosaki
authors.affiliation: Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cahan
authors.affiliation: Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Dong I
authors.initials: DI
authors.lastname: Lee
authors.affiliation: Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Johns Hopkins Institute for Cell Engineering, Baltimore, MD 21205, USA.
authors.forename: Songnan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Johns Hopkins Institute for Cell Engineering, Baltimore, MD 21205, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Miyamoto
authors.affiliation: Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Johns Hopkins Institute for Cell Engineering, Baltimore, MD 21205, USA.
authors.forename: Laviel
authors.initials: L
authors.lastname: Fernandez
authors.affiliation: Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Kass
authors.affiliation: Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Johns Hopkins Institute for Cell Engineering, Baltimore, MD 21205, USA. Electronic address: ckwon13@jhmi.edu.
authors.forename: Chulan
authors.initials: C
authors.lastname: Kwon
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology; D015870:Gene Expression / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D014157:Transcription Factors