title: Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature.
abstract: Cardiomyocytes derived from pluripotent stem cells can be applied in drug testing, disease modeling and cell-based therapy. However, without procardiogenic growth factors, the efficiency of cardiomyogenesis from pluripotent stem cells is usually low and the resulting cardiomyocyte population is heterogeneous. Here, we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes (VMs), and consistent with other reports of iPSCs derived from various somatic cell types, VM-derived iPSCs (ViPSCs) exhibit a markedly higher propensity to spontaneously differentiate into beating cardiomyocytes as compared to genetically matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts. Strikingly, the majority of ViPSC-derived cardiomyocytes display a ventricular phenotype. The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation. In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs, we performed global gene expression and DNA methylation analysis, which revealed a distinct epigenetic signature that may be involved in specifying the VM fate in pluripotent stem cells.
authors: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
authors: Huansheng
authors: H
authors: Xu
authors: B Alexander
authors: BA
authors: Yi
authors: Hao
authors: H
authors: Wu
authors: Christoph
authors: C
authors: Bock
authors: Hongcang
authors: H
authors: Gu
authors: Kathy O
authors: KO
authors: Lui
authors: Joo-Hye C
authors: JH
authors: Park
authors: Ying
authors: Y
authors: Shao
authors: Alyssa K
authors: AK
authors: Riley
authors: Ibrahim J
authors: IJ
authors: Domian
authors: Erding
authors: E
authors: Hu
authors: Robert
authors: R
authors: Willette
authors: John
authors: J
authors: Lepore
authors: Alexander
authors: A
authors: Meissner
authors: Zhong
authors: Z
authors: Wang
authors: Kenneth R
authors: KR
authors: Chien
mesh_terms: D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002678:Chimera / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D044127:Epigenesis, Genetic; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D024510:Muscle Development; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000502:physiology