title: Determination of the human cardiomyocyte mRNA and miRNA differentiation network by fine-scale profiling.
abstract: To gain insight into the molecular regulation of human heart development, a detailed comparison of the mRNA and miRNA transcriptomes across differentiating human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts was performed. Gene ontology analysis of the mRNA expression levels of the hiPSCs differentiating into cardiomyocytes revealed 3 distinct groups of genes: pluripotent specific, transitional cardiac specification, and mature cardiomyocyte specific. Hierarchical clustering of the mRNA data revealed that the transcriptome of hiPSC cardiomyocytes largely stabilizes 20 days after initiation of differentiation. Nevertheless, analysis of cells continuously cultured for 120 days indicated that the cardiomyocytes continued to mature toward a more adult-like gene expression pattern. Analysis of cardiomyocyte-specific miRNAs (miR-1, miR-133a/b, and miR-208a/b) revealed an miRNA pattern indicative of stem cell to cardiomyocyte specification. A biostatistitical approach integrated the miRNA and mRNA expression profiles revealing a cardiomyocyte differentiation miRNA network and identified putative mRNAs targeted by multiple miRNAs. Together, these data reveal the miRNA network in human heart development and support the notion that overlapping miRNA networks re-enforce transcriptional control during developmental specification.
authors: Nonclinical Safety, Hoffmann-La Roche, Nutley, New Jersey 07110, USA.
authors: Joshua E
authors: JE
authors: Babiarz
authors: Morgane
authors: M
authors: Ravon
authors: Sriram
authors: S
authors: Sridhar
authors: Palanikumar
authors: P
authors: Ravindran
authors: Brad
authors: B
authors: Swanson
authors: Hans
authors: H
authors: Bitter
authors: Thomas
authors: T
authors: Weiser
authors: Eric
authors: E
authors: Chiao
authors: Ulrich
authors: U
authors: Certa
authors: Kyle L
authors: KL
authors: Kolaja
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D005333:Fetus / Q000166:cytology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006321:Heart / Q000254:growth & development; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012333:RNA, Messenger