Sunny Sini, Challa Anil Kumar, Qiao Aijun, Jyothidasan Arun, Krishnamurthy Prasanna, Ramamurthy Muralidharan T, Crossman David K, Pogwizd Steven, Cinghu Senthilkumar, Rajasekaran Namakkal S
Department of Pathology, University of Alabama at Birmingham, AL, USA.
Department of Biomedical Engineering, University of Alabama at Birmingham, AL, USA.
Cardiol Cardiovasc Med. 2021;5(5):454-470. doi: 10.26502/fccm.92920215. Epub 2021 Sep 7.
The development of the heart follows a synergic action of several signaling pathways during gestational, pre- & postnatal stages. The current study aimed to investigate whether the myocardium experiences transcriptional changes during the transition from post-natal to adult hood stages. Herein, we used C57/B16/J mice at 4 (28- days; post-natal/PN) and 20 weeks (adulthood/AH) of ages and employed the next generation RNAseq (NGS) to profile the transcriptome and echocardiography analysis to monitor the structural/functional changes in the heart. NGS-based RNA-seq revealed that 1215 genes were significantly upregulated and 2549 were down regulated in the AH versus PN hearts, indicating a significant transcriptional change during this transition. A synchronized cardiac transcriptional regulation through cell cycle, growth hormones, redox homeostasis and metabolic pathways was noticed in both PN and AH hearts. Echocardiography reveals significant structural and functional (i.e. systolic/diastolic) changes during the transition of PN to adult stage. Particularly, a progressive decline in ejection fraction and cardiac output was observed in AH hearts. These structural adaptations are in line with critical signaling pathways that drive the maturation of heart during AH. Overall, we have presented a comprehensive transcriptomic analysis along with structural-functional relationship during the myocardial development in adult mice.
在妊娠、出生前和出生后阶段，心脏的发育遵循多种信号通路的协同作用。本研究旨在调查心肌在从出生后到成年阶段的转变过程中是否经历转录变化。在此，我们使用了4周龄（28天；出生后/PN）和20周龄（成年/AH）的C57/B16/J小鼠，并采用下一代RNA测序（NGS）来分析转录组，以及使用超声心动图分析来监测心脏的结构/功能变化。基于NGS的RNA测序显示，与PN期心脏相比，AH期心脏中有1215个基因显著上调，2549个基因下调，表明在此转变过程中存在显著的转录变化。在PN期和AH期心脏中均发现了通过细胞周期、生长激素、氧化还原稳态和代谢途径进行的同步心脏转录调控。超声心动图显示，在从PN期到成年期的转变过程中，心脏存在显著的结构和功能（即收缩/舒张）变化。特别是，在AH期心脏中观察到射血分数和心输出量逐渐下降。这些结构适应性变化与驱动AH期心脏成熟的关键信号通路一致。总体而言，我们展示了成年小鼠心肌发育过程中的全面转录组分析以及结构-功能关系。
