Novel insights into cardiac regeneration based on differential fetal and adult ovine heart transcriptomic analysis

BELAICH, MARIANO NICOLÁS; URANGA VEGA, MARTÍN; BAUZÁ, MARÍA DEL ROSARIO; CROTTOGINI, ALBERTO; LOCATELLI, PAOLA; OLEA, FERNANDA DANIELA; SIMONIN, ALEJANDRO; CUNIBERTI, LUIS; GHIRINGHELLI, DANIEL; LÓPEZ AYELÉN EMILCE; GIMÉNEZ, CARLOS SEBASTIÁN; CASTILLO, MARTHA GIOVANNA; CERRUDO, CAROLINA; BELAICH, MARIANO NICOLÁS; URANGA VEGA, MARTÍN; BAUZÁ, MARÍA DEL ROSARIO; CROTTOGINI, ALBERTO; LOCATELLI, PAOLA; OLEA, FERNANDA DANIELA; SIMONIN, ALEJANDRO; CUNIBERTI, LUIS; GHIRINGHELLI, DANIEL; LÓPEZ AYELÉN EMILCE; GIMÉNEZ, CARLOS SEBASTIÁN; CASTILLO, MARTHA GIOVANNA; CERRUDO, CAROLINA

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2020 p. 1 - 46

0363-6135

The adult mammalian cardiomyocyte has a very limited capacity to re-enter the cell cycle and advance into mitosis. Therefore, diseases characterized by lost contractile tissue usually evolve into myocardial remodeling and heart failure. Analyzing the cardiac transcriptome at different developmental stages in a large mammal closer to the human than laboratory rodents may serve to disclose positive and negative cardiomyocyte cell cycle regulators potentially targetable to induce cardiac regeneration in the clinical setting. We thus aimed at characterizing the transcriptomic profiles of the early fetal, late fetal and adult sheep heart employing RNA-seq technique and bioinformatic analysis to detect protein encoding genes that in some of the stages were turned-off, turned-on or differentially expressed. Genes earlier proposed as positive cell cycle regulators such as cyclin A, cdk2, meis2, meis3 and PCNA showed higher expression in fetal hearts and lower in AH, as expected. In contrast, genes previously proposed as cell cycle inhibitors such as meis1, p16 and sav1 tended to be higher in fetal than in adult hearts, suggesting that these genes are involved in cell processes other than cell cycle regulation. Additionally, we described Gene Ontology (GO) enrichment of different sets of genes. GO analysis revealed that differentially expressed gene sets were mainly associated with metabolic and cellular processes. The cell cycle-related genes fam64a, cdc20 and cdk1, and the metabolism-related genes pitx and adipoq showed strong differential expression between fetal and adult hearts, thus being potent candidates to be targeted in human cardiac regeneration strategies.