We have shown that when permanent occlusion of left anterior descending coronary artery surgery is performed in newborn large mammals (pigs) on postnatal day 1 (P1), 1 the animals can recover completely from a myocardial infarction (MI) that occurs on postnatal day 28 (P28) with no evidence of scarring or decline in contractile performance. 2 Our results also suggested that cardiac apical resection (AR) on P1 preserved cardiomyocyte cell cycle activity as the animals aged; thus, we analyzed single-nucleus RNA sequencing data sets to compare the transcriptomes of cardiomyocytes from fetal pigs (embryonic day 80) with those from pigs that underwent AR surgery on P1 (ARP1), AR surgery on P1 followed by left anterior descending coronary artery occlusion MI induction on P28 (ARP1MIP28), MI on P28 without previous AR (MIP28), or neither surgical procedure (controls). Hearts from ARP1MIP28 animals were explanted from postnatal day 30 (P30) through postnatal day 56 (P56) and hearts from all other groups were explanted on P1, P28, or P56 (Figure [A–D]). All experimental protocols were approved by the Institutional Animal Care and Use Committee of the University of Alabama at Birmingham and performed under the National Institutes of Health Guide for the Care and Use of Laboratory Animals. University of Alabama at Birmingham is licensed as an animal research facility (64-R-0004) by the US Department of Agriculture and has an Animal Welfare Assurance (A3255-01) on file with the Office of Laboratory Animal Welfare. Data were processed using the Seurat toolkit, latent representations of single nuclei were obtained with scvitools, and dimension reduction was performed using uniform manifold approximation and projection. All single-cell transcriptomic data, including the raw and processed files, are publicly available at Gene Expression Omnibus (accession number, GSE185289; URL: https://www. ncbi. nlm. nih. gov/geo/query/acc. cgi? acc= GSE185289). A total of 218 945 high-quality nuclei were captured and Louvain clustering analysis for known lineage markers identified all 8 major cardiac cell types (Figure [E]). The Figure (Ei) shows that most of the noncardiomyocyte clusters contain nuclei from all heart samples regardless of the treatment or age, indicating limited variation between different batches of sample collections. Complete gene nucleus data were available for 94 844 cardiomyocytes and variations between the anterior apical zone and the remote zone within each group were negligible when compared with variations between groups. Cardiomyocytes were distributed among 6 clusters (cardiomyocyte 1–cardiomyocyte 6; Figure [F]). Three of the clusters were almost entirely composed of cardiomyocytes from a single experimental group (cardiomyocyte 2 [96.2% control–P56], cardiomyocyte 3