RNA expression in postnatal mouse ventricular tissue

Mammals lose the ability to regenerate their hearts within one week after birth. During this regenerative window, cardiac energy metabolism shifts from glycolysis to fatty acid oxidation, and recent evidence suggests that metabolism may participate in controlling cardiomyocyte cell cycle. However, the molecular mechanisms mediating the loss of postnatal cardiac regeneration are not fully understood. This study aims at providing an integrated resource of mRNA, protein and metabolite changes in the neonatal heart to identify metabolism-related mechanisms associated with the postnatal loss of regenerative capacity. Mouse ventricular tissue samples taken on postnatal days 1, 4, 9 and 23 (P01, P04, P09 and P23, respectively) were analyzed with RNA sequencing (RNAseq) and global proteomics and metabolomics. Differential expression was observed for 8547 mRNAs and for 1199 of the 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Gene ontology analysis, KEGG pathway analysis and fuzzy c-means clustering were used to identify biological processes and metabolic pathways either up- or downregulated on all three levels. This is the first systems-level resource combining data from genome-wide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses of the mouse heart throughout the early postnatal period. This integrated multi-level data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies. RNA sequencing was carried out with three pooled samples (each from 3 hearts) at each time point - i.e. 1, 4, 9 and 23 days after birth.哺乳动物在出生后一周内便会丧失心脏再生能力。在此再生窗口期内，心脏能量代谢模式会从糖酵解转向脂肪酸氧化；近期研究证据表明，代谢过程可能参与调控心肌细胞周期。然而，介导出生后心脏再生能力丧失的分子机制尚未完全阐明。本研究旨在构建新生小鼠心脏中mRNA、蛋白质及代谢物变化的整合数据集，以挖掘与出生后再生能力丧失相关的代谢调控机制。本研究对出生后第1、4、9、23天（分别记为P01、P04、P09及P23）的小鼠心室组织样本进行了RNA测序（RNAseq）、全局蛋白质组学及代谢组学分析。共计8547条mRNA、2285种定量蛋白质中的1199种呈现显著差异表达；此外还鉴定出151种发生显著变化的代谢物。研究通过基因本体（Gene Ontology）分析、京都基因与基因组百科全书（KEGG）通路分析及模糊C均值聚类，鉴定出在三个组学层面均出现上调或下调的生物学过程与代谢通路。这是首个整合全基因组转录组、全局定量蛋白质组及非靶向代谢组数据的小鼠出生后早期心脏系统级数据集。这套与心脏再生能力丧失相关的多维度分子变化整合数据集，有望为再生治疗的开发提供全新思路。每个时间点均设置3份混合样本（每份样本取自3颗心脏）用于RNA测序，对应时间为出生后1、4、9及23天。