Congratulation to lab members Thanh Nguyen, Yuhua Wei and Yuji Nakada. They will present in AHA Scientific Session 2022.

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Single-nucleus RNA Sequencing Analysis Reveals Subpopulation of Endothelial Cells Activation in Hearts of Porcine Double Injury Model

 

Pigs underwent double injury model of apical resection on neonatal day 1 (ARP1) and LAD ligation on postnatal day 28 (MIP28), can remuscularize the AMI by postnatal day56 (P56) with little evidence of myocardial scarring, which is accompanied by increased cardiomyocytes (CM) cell-cycle activity. The vascularization occurred to support remuscularization has not been studied. Therefore, we analyze the single-nucleus RNA sequencing (snRNA-seq) data, collected from the MI-border zone of ARP1-MIP28, MIP28 (without ARP1), naïve, and fetal pig endothelial cells (EC), using the Artificial Intelligence autoencoder and cluster analyses. Three clusters of EC cells were identified. Among them, vascular and lymphatic EC clusters (denoted EC1 and EC2 in figure 1) were presented and in all postnatal hearts. Besides expressing vascular EC gene signatures, the remaining cluster, named ‘EC3’, also upregulated Transforming grow factor beta (TGFβ) and Bone Morphogenetic Proteins (BMP) signaling markers. These signaling markers indicated EC3 were still under development. EC3 strongly presented in the fetal heart, where its proportion was 31% of ECs; then, EC3 proportions decreased as the pig matured and virtually dismissed (<2%) in naïve heart from P28 to later. Up to 1 weeks following MIP28 injury, EC3 proportions remained low (<2%) in MIP28-only hearts; meanwhile, EC3 proportions significantly increased (>7%) in the regenerative ARP1-MIP28 hearts. Thus, in the ARP1-MIP28 injured hearts, subpopulation of EC3 is activated to support the remuscularization.