Wang Sheng-Nan, Tian Wen-Jie, Pan Deng-Ke, Hai Tang, Ma Yue-Hui, Wang Dan-Dan, Jiang Lin
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
Institute of Organ Transplantation, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
Zool Res. 2025 May 18;46(3):634-646. doi: 10.24272/j.issn.2095-8137.2024.348.
Pigs have emerged as valuable large-animal models for cardiac xenotransplantation; however, the temporal dynamics of myocardial development in this species remains insufficiently defined. This study analyzed gene expression patterns across four key developmental stages (neonatal, juvenile, sexual maturity, and adulthood) to delineate the molecular mechanisms driving porcine myocardial development. Increases in heart weight were accompanied by proportional expansion of myocardial fiber area and chamber size, reflecting coordinated structural development. Transcriptomic profiling of myocardial tissue by RNA sequencing (RNA-seq) identified 2 189 differentially expressed genes (DEGs) across stage comparisons. Short time-series expression miner (STEM) analysis classified these DEGs into four major expression clusters enriched in pathways associated with myocardial development, immune responses, cell proliferation, and metabolic processes. Among 359 DEGs conserved across all developmental stages, six candidate genes were strongly associated with myocardial development. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) confirmed a significant correlation between the expression of these candidate genes and myocardial development in porcine tissue. These findings establish a transcriptomic framework for porcine myocardial maturation and provide a molecular basis for advancing cardiac xenotransplantation.
猪已成为心脏异种移植中有价值的大型动物模型;然而,该物种心肌发育的时间动态仍未得到充分界定。本研究分析了四个关键发育阶段(新生儿期、幼年期、性成熟期和成年期)的基因表达模式,以阐明驱动猪心肌发育的分子机制。心脏重量的增加伴随着心肌纤维面积和腔室大小的成比例扩大,反映了结构的协调发育。通过RNA测序(RNA-seq)对心肌组织进行转录组分析,在各阶段比较中鉴定出2189个差异表达基因(DEG)。短时序列表达挖掘器(STEM)分析将这些DEG分为四个主要表达簇,这些簇富含与心肌发育、免疫反应、细胞增殖和代谢过程相关的通路。在所有发育阶段保守的359个DEG中,六个候选基因与心肌发育密切相关。逆转录定量实时聚合酶链反应(RT-qPCR)证实了这些候选基因的表达与猪组织中心肌发育之间存在显著相关性。这些发现建立了猪心肌成熟的转录组框架,并为推进心脏异种移植提供了分子基础。