GSE185289
Single nucleus transcriptomics: Apical resection in newborn pigs extends the time-window of cardiomyocyte proliferation and myocardial regeneration
Background: In this study, we have extended the myocardial regenerative window to postnatal day 28 (P28) by a double injury pig model (ARP1MIP28) of apical resection at P1 (ARP1) and LAD ligation at P28 (MIP28). However, the molecular mechanism of regenerative window extension is not known. Results: Gene-expression profiles revealed that regenerating ARP1MIP28 hearts contained different subpopulations of cardiomyocytes early after 2nd injury. The six cardiomyocyte clusters were identified (CM1-CM6) by Louvain clustering. The CM6, CM3, and CM2 clusters have mainly consisted of fetal (92.4%), CTL-P1 (95.7%), and CTL-P56 (96.2%) cardiomyocytes. In contrast, the CM1 cluster has consisted of heterogeneous cardiomyocyte groups from all other animal groups, including less than 1% of fetal and CTL-P1 cardiomyocytes. The CM5 and CM4 clusters have mainly consisted of ARP1MIP28-P35 cardiomyocytes, 97.8%, and 68.6%, respectively. Sparse modeling analysis revealed that AR and MI injury, both alone and in combination, appeared to promote the proliferative capacity of cardiomyocytes and perturb cardiomyocyte maturation. Publication: This dataseries is associated to manuscript titled 'Single nucleus transcriptomics: Apical resection in newborn pigs extends the time-window of cardiomyocyte proliferation and myocardial regeneration', published in Circulation, 2021. Overall design: The ARP1-MIP28 pig hearts demonstrated no visible myocardial structural or functional damage 4 weeks after LAD ligation. Here, ARP1 means that the pig heart received apical resection on postnatal day 1, and MIP28 means that the pig heart received LAD ligation on postnatal day 28. The nuclear RNA contents were isolated from pig hearts that received regenerative or non-regenerative types of cardiac surgery and performed snRNA-seq to characterize gene-expression profile of the ARP1MIP28 in cardiomyocytes. The study includes the following groups: FH, CTL-P1, CTL-P28, CTL-P56, ARP1-P28, ARP1-P56, MIP28-P56, ARP1-MIP28-P30, ARP1-MIP28-P35, ARP1-MIP28-P42, and ARP1-MIP28-P56. Here, FH means fetal heart, CTL means naïve postnatal heart (no injury), P1/P28/P30/P35/P42/P56 means the postnatal day (1/28/30/35/42/56, correspondingly) when the pig heart tissue was harvested and sent to single-nuclei sequencing.