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RNA-Binding Protein Signature in Proliferative Cardiomyocytes: A Cross-Species Meta-Analysis from Mouse, Pig, and
Thanh Nguyen1, Kaili Hao1, Yuji Nakada1
1Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Biomolecules
|February 26, 2025
Summary
Understanding RNA-binding proteins (RBPs) is key to heart repair. This study found specific RBPs are crucial for cardiomyocyte proliferation in mammals, offering new avenues for cardiovascular research and regenerative medicine.
Area of Science:
- Cardiovascular Sciences
- Molecular Biology
- Regenerative Medicine
Background:
- Mammalian cardiomyocyte cell-cycle withdrawal after birth limits heart repair following myocardial injury.
- Neonatal mammals can regenerate myocardium after injury due to cardiomyocyte proliferation.
- RNA-binding proteins (RBPs) regulate the translation of cell-cycle machinery mRNA, impacting proliferation.
Purpose of the Study:
- To investigate the relationship between RNA-binding protein (RBP) expression and cardiomyocyte proliferation.
- To identify conserved RBPs associated with cardiomyocyte proliferation across species.
Main Methods:
- Meta-analysis of single-nuclei RNA sequencing (snRNA-seq) data from regenerating mouse and pig hearts using an Autoencoder.
- Bulk RNA sequencing (RNA-seq) analysis of human-induced pluripotent stem cell-derived (hiPSC) cardiomyocyte (hiPSC-CM) cell lines at different proliferation stages.
- Cross-species comparison of RBP expression in proliferating cardiomyocytes.
Main Results:
- Twenty-one RBPs were consistently upregulated, and six were downregulated in proliferating cardiomyocytes across mouse, pig, and hiPSC-CM models.
- Immunofluorescence validated increased protein levels of DHX9, PTBP3, HNRNPUL1, and DDX6 in proliferating pig cardiomyocytes.
- A strong association between RBP expression and cardiomyocyte proliferation was demonstrated across species.
Conclusions:
- Specific RNA-binding proteins play a conserved role in regulating cardiomyocyte proliferation.
- These findings highlight RBPs as potential targets for promoting heart regeneration.
- The study provides a foundation for developing novel therapeutic strategies for cardiovascular diseases.
