10.1371/journal.pone.0133288
Jingyi Gan
Jingyi
Gan
Hans-Joachim Sonntag
Hans-Joachim
Sonntag
Mei kuen Tang
Mei kuen
Tang
Dongqing Cai
Dongqing
Cai
Kenneth Ka Ho Lee
Kenneth
Ka Ho Lee
Integrative Analysis of the Developing Postnatal Mouse Heart Transcriptome
Public Library of Science
2015
bioinformatics analysis
Regulator Effects network analysis
growth arrest
gene ontology
ipa
heart tissues
microarray analysis
gene ontology categories
gata
transcriptional regulation
gene interaction networks
Postnatal Mouse Heart Transcriptome
Functional annotation
cardiomyocyte exit
IGF 1R
postnatal heart development
infarcted heart
myh
tasp
dna
mouse hearts
cardiomyocyte proliferation
Ingenuity Pathways Analysis
interaction networks
tob
aif
Integrative analysis
enrichment analyses
postnatal mouse hearts
KEGG pathway
cell cycle
TFF
2015-07-22 02:59:17
Dataset
https://plos.figshare.com/articles/dataset/_Integrative_Analysis_of_the_Developing_Postnatal_Mouse_Heart_Transcriptome_/1491708
<div><p>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.</p></div>