TY - DATA T1 - Integrative Analysis of the Developing Postnatal Mouse Heart Transcriptome PY - 2015/07/22 AU - Jingyi Gan AU - Hans-Joachim Sonntag AU - Mei kuen Tang AU - Dongqing Cai AU - Kenneth Ka Ho Lee UR - https://plos.figshare.com/articles/dataset/_Integrative_Analysis_of_the_Developing_Postnatal_Mouse_Heart_Transcriptome_/1491708 DO - 10.1371/journal.pone.0133288 L4 - https://ndownloader.figshare.com/files/2186488 L4 - https://ndownloader.figshare.com/files/2186489 L4 - https://ndownloader.figshare.com/files/2186490 L4 - https://ndownloader.figshare.com/files/2186491 L4 - https://ndownloader.figshare.com/files/2186492 L4 - https://ndownloader.figshare.com/files/2186494 KW - bioinformatics analysis KW - Regulator Effects network analysis KW - growth arrest KW - gene ontology KW - ipa KW - heart tissues KW - microarray analysis KW - gene ontology categories KW - gata KW - transcriptional regulation KW - gene interaction networks KW - Postnatal Mouse Heart Transcriptome KW - Functional annotation KW - cardiomyocyte exit KW - IGF 1R KW - postnatal heart development KW - infarcted heart KW - myh KW - tasp KW - dna KW - mouse hearts KW - cardiomyocyte proliferation KW - Ingenuity Pathways Analysis KW - interaction networks KW - tob KW - aif KW - Integrative analysis KW - enrichment analyses KW - postnatal mouse hearts KW - KEGG pathway KW - cell cycle KW - TFF N2 - In mammals, cardiomyocytes rapidly proliferate in the fetus and continue to do so for a few more days after birth. These cardiomyocytes then enter into growth arrest but the detailed molecular mechanisms involved have not been fully elucidated. We have addressed this issue by comparing the transcriptomes of 2-day-old (containing dividing cardiomyocytes) with 13-day-old (containing growth arrested cardiomyocytes) postnatal mouse hearts. We performed comparative microarray analysis on the heart tissues and then conducted Functional annotation, Gene ontology, KEGG pathway and Gene Set enrichment analyses on the differentially expressed genes. The bioinformatics analysis revealed that gene ontology categories associated with the “cell cycle”, “DNA replication”, “chromosome segregation” and “microtubule cytoskeleton” were down-regulated. Inversely, “immune response”, “extracellular matrix”, “cell differentiation” and “cell membrane” were up-regulated. Ingenuity Pathways Analysis (IPA) has revealed that GATA4, MYH7 and IGF1R were the key drivers of the gene interaction networks. In addition, Regulator Effects network analysis suggested that TASP1, TOB1, C1orf61, AIF1, ROCK1, TFF2 and miR503-5p may be acting on the cardiomyocytes in 13-day-old mouse hearts to inhibit cardiomyocyte proliferation and G1/S phase transition. RT-qPCR was used to validate genes which were differentially expressed and genes that play a prominent role in the pathways and interaction networks that we identified. In sum, our integrative analysis has provided more insights into the transcriptional regulation of cardiomyocyte exit from the cell cycle during postnatal heart development. The results also pinpoint potential regulators that could be used to induce growth arrested cardiomyocytes to proliferate in the infarcted heart. ER -