Chamber-Specific Transcriptomic Insight into Cardiac Development using Guinea Pig and Human Heart Tissue

Document Type

Journal Article

Publication Date

11-6-2025

Journal

Physiological genomics

DOI

10.1152/physiolgenomics.00212.2025

Keywords

Atria; Cardiac Maturation; Guinea Pig; Humans; Transcriptomics

Abstract

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., Cdk1, Cdk2) and glycogen energy metabolism genes (e.g., Irs1, Akt2), whereas adults overexpressed calcium signaling genes (e.g., Sln, Casq2). Second, we compared the transcriptional profile of right atria and left ventricular tissue; atrial maturation was enriched for sinoatrial node and conduction system pathways, while 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 S100A1, SLN, and MYL4, 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.

Department

Pediatrics

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