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Tissue-specific miRNA Expression Profiling in Mouse Heart Sections Using In Situ Hybridization
Published on: September 15, 2018
Sexual dimorphisms of mRNA and miRNA in human/murine heart disease
Masato Tsuji1,2, Takanori Kawasaki3, Takeru Matsuda4
1Division of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical Dental University, Tokyo, Japan.
Insights
The male and female heart transcriptome shows significant sex differences in both healthy and diseased states. Understanding these genetic differences is key to developing gender-specific cardiac treatment strategies.
Area of Science:
- Cardiovascular Biology
- Genomics
- Molecular Biology
Background:
- Sexual dimorphisms are evident in cardiac diseases like ischemic cardiomyopathy (ICM), hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM).
- Understanding sex-specific genetic programs is vital for tailored treatment strategies.
- This study comprehensively analyzes sex differences in the heart transcriptome.
Purpose of the Study:
- To characterize sexual dimorphisms in the healthy and diseased heart.
- To investigate differences at the mRNA and miRNA transcriptome levels.
- To lay the foundation for gender-specific cardiac treatment strategies.
Main Methods:
- Meta-analysis and microarray analysis of existing mRNA data from mouse and human hearts.
- Microarray analysis of miRNA from mouse and human heart samples (sham/MI and normal/ICM).
- Integration of transcriptome data to identify sexually dimorphic genes and miRNAs.
Main Results:
- Dozens/hundreds of sexually dimorphic genes identified in healthy and diseased hearts (ICM, HCM, DCM).
- Sexually dimorphic genes are enriched in ontologies related to cardiac homeostasis.
- Sexually dimorphic miRNAs identified in both mouse (MI and normal) and human (ICM and normal) hearts, revealing miRNA-mRNA networks with sex-biased operation.
Conclusions:
- Significant sex differences exist in the mRNA and miRNA transcriptome of normal and diseased hearts.
- These differences may impact cardiac homeostasis.
- Provides a comprehensive genome-wide view of heart sexual dimorphisms, supporting gender-specific therapies.
Background:
Sexual dimorphisms are well recognized in various cardiac diseases such as ischemic cardiomyopathy (ICM), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Thorough understanding of the underlying genetic programs is crucial to optimize treatment strategies specified for each gender. By performing meta-analysis and microarray analysis, we sought to comprehensively characterize the sexual dimorphisms in the healthy and diseased heart at the level of both mRNA and miRNA transcriptome.
Results:
Existing mRNA microarray data of both mouse and human heart were integrated, identifying dozens/ hundreds of sexually dimorphic genes in healthy heart, ICM, HCM, and DCM. These sexually dimorphic genes overrepresented gene ontologies (GOs) important for cardiac homeostasis. Further, microarray of miRNA, isolated from mouse sham left ventricle (LV) (n = 6 & n = 5 for male & female) and chronic MI LV (n = 19 & n = 19) and from human normal LV (n = 6 & n = 6) and ICM LV (n = 4 & n = 5), was conducted. This revealed that 13 mouse miRNAs are sexually dimorphic in MI and 6 in normal heart. In human, 3 miRNAs were sexually dimorphic in ICM and 15 in normal heart. These data revealed miRNA-mRNA networks that operate in a sexually-biased fashion.
Conclusions:
mRNA and miRNA transcriptome of normal and disease heart show significant sex differences, which might impact the cardiac homeostasis. Together this study provides the first comprehensive picture of the genome-wide program underlying the heart sexual dimorphisms, laying the foundation for gender specific treatment strategies.
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