Adult mammalian cardiomyocytes have very limited capacity to proliferate and repair the myocardial infarction. However, when apical resection (AR) was performed in pig hearts on postnatal day (P) 1 (AR) and acute myocardial infarction (MI) was induced on P28 (MI), the animals recovered with no evidence of myocardial scarring or decline in contractile performance. Furthermore, the repair process appeared to be driven by cardiomyocyte proliferation, but the regulatory molecules that govern the AR-induced enhancement of myocardial recovery remain unclear. Single-nucleus RNA sequencing (snRNA-seq) data collected from fetal pig hearts and the hearts of pigs that underwent AR, MI, both AR and MI, or neither myocardial injury were evaluated autoencoder, cluster analysis, sparse learning, and semisupervised learning. Ten clusters of cardiomyocytes (CM1-CM10) were identified across all experimental groups and time points. CM1 was only observed in AR hearts on P28 and was enriched for the expression of T-box transcription factors 5 and 20 (TBX5 and TBX20, respectively), Erb-B2 receptor tyrosine kinase 4 (ERBB4), and G Protein-Coupled Receptor Kinase 5 (GRK5), as well as genes associated with the proliferation and growth of cardiac muscle. CM1 cardiomyocytes also highly expressed genes for glycolysis while lowly expressed genes for adrenergic signaling, which suggested that CM1 were immature cardiomyocytes. Thus, we have identified a cluster of cardiomyocytes, CM1, in neonatal pig hearts that appeared to be generated in response to AR injury on P1 and may have been primed for activation of CM cell-cycle activation and proliferation by the upregulation of TBX5, TBX20, ERBB4, and GRK5.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289371PMC
http://dx.doi.org/10.3389/fbioe.2022.914450DOI Listing

Publication Analysis

Top Keywords

pig hearts
12
myocardial infarction
8
tbx5 tbx20
8
expressed genes
8
cardiomyocytes
5
myocardial
5
hearts
5
cardiomyocyte cell-cycle
4
cell-cycle regulation
4
regulation neonatal
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!