Transcriptomic analysis indicates a role for oxidative phosphorylation in postnatal development of rat carotid body hypoxic sensitivity

The carotid body (CB), located bilaterally at the carotid artery bifurcations, is the primary sensory organ for monitoring arterial blood O2 levels. Carotid bodies are immature at birth, exhibiting low sensitivity to hypoxia and become more sensitive with maturation during the first few weeks of neonatal life. To understand the molecular basis for the postnatal developmental hypoxic responses of CB, we isolated CBs from 5-day and 21-day-old Sprague Dawley rats, and performed RNA-sequencing, which allows comprehensive analysis of gene expression. Differentially expressed genes (DEGs) were generated using Edge R, while functional enrichment analysis was performed using GSEA. Analysis of RNA seq data showed 1769 DEGs of the total 12,696 genes shared between neonates and adults. Of the 1769 DEGs, 924 genes were upregulated, and 1680 genes were downregulated. Further analysis showed that genes related to oxidative phosphorylation (Ox/phos) and hypoxia-signaling pathways were significantly upregulated in neonatal compared to adult CBs, suggesting a possible link to differential developmental hypoxic responses seen in CB. Genes related to cytokine signaling (INF and TNFα) and transcription factors (CREB and NFB) mediated pathways were enriched in adult CBs suggesting expression of these pathways may be linked to developmental regulation. The RNA-seq results were verified by analyzing mRNA changes in selected genes by qRT-PCR. Our results of enrichment analysis of biological pathways offer a valuable insight into CB hypoxic sensing responses and development process.颈动脉体（carotid body, CB）双侧分布于颈动脉分叉处，是监测动脉血氧水平的主要感觉器官。颈动脉体在出生时尚未发育成熟，对缺氧的敏感性较低，并在新生期的最初数周内随着成熟进程逐步提升敏感性。为阐明颈动脉体出生后发育性缺氧应答的分子基础，我们从5日龄和21日龄的斯普拉格-道利（Sprague Dawley）大鼠体内分离颈动脉体，开展RNA测序（RNA-sequencing），该技术可实现基因表达的全面分析。本研究采用Edge R筛选差异表达基因（differentially expressed genes, DEGs），并通过基因集富集分析（Gene Set Enrichment Analysis, GSEA）完成功能富集分析。RNA测序数据分析显示，在新生鼠与成年鼠共有的12696个基因中，共鉴定出1769个差异表达基因；其中924个基因上调，1680个基因下调。进一步分析表明，相较于成年颈动脉体，新生鼠颈动脉体中与氧化磷酸化（oxidative phosphorylation, Ox/phos）及缺氧信号通路相关的基因显著上调，提示该特征可能与颈动脉体发育性缺氧应答的差异存在关联。而与细胞因子信号通路（包含INFγ及TNFα）及转录因子（CREB与NFκB）介导的通路相关的基因在成年颈动脉体中富集，表明这些通路的表达或参与发育调控过程。本研究通过qRT-PCR分析选定基因的mRNA表达变化，验证了RNA测序的结果。本研究的生物学通路富集分析结果，为颈动脉体缺氧感知应答与发育进程的研究提供了极具价值的见解。