Chamber-specific transcriptomic insight into cardiac development using guinea pig and human heart tissue

The heart undergoes significant molecular and functional adaptations throughout postnatal development. However, our understanding of these dynamic changes in the human heart is limited. Advances in pediatric cardiac research are often hindered by the lack of preclinical models. Guinea pigs may serve as a useful model for human cardiac research, as the guinea pig and human myocardium have similar ion channel expression and cardiovascular drug responsiveness. Yet, gene expression patterns during postnatal heart development have not been comprehensively investigated. In this study, we first characterized transcriptional changes in neonatal, juvenile, and adult guinea pig hearts. Neonatal hearts overexpressed cell-cycle (e.g., <i>Cdk1</i>, <i>Cdk2</i>) and glycogen energy metabolism genes (e.g., <i>Irs1</i>, <i>Akt2</i>), whereas adults overexpressed calcium signaling genes (e.g., <i>Sln</i>, <i>Casq2</i>). Second, we compared the transcriptional profile of right atria and left ventricular tissue; atrial maturation was enriched for sinoatrial node and conduction system pathways, whereas ventricular maturation was enriched for sarcomere organization and action potential regulation. Finally, we conducted a cross-species comparison of the right atrial transcriptome between humans and guinea pigs. This identified conserved maturation markers, including <i>S100A1</i>, <i>SLN</i>, and <i>MYL4</i>, suggesting shared temporal gene expression programs during postnatal cardiac development. Our findings provide a molecular framework for understanding age- and chamber-specific cardiac development, supporting the guinea pig as a promising preclinical model for studying human heart maturation. By identifying conserved gene programs and developmental markers across species, this study lays the groundwork for age-specific pharmacological strategies and computational models that can help to refine treatment decisions for pediatric patients.<b>NEW & NOTEWORTHY</b> Existing knowledge on postnatal heart development and cardiomyocyte maturation is limited. We investigated age-dependent transcriptional changes in neonatal, juvenile, and adult guinea pig hearts and then conducted a cross-species comparison to identify age-specific patterns that are conserved in the guinea pig and human atria. Expanding our knowledge of chamber- and age-specific gene expression patterns can inform and guide the selection of cardiovascular therapies in the pediatric population, where developmental differences are understudied.