Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, The University of Chicago, Chicago, IL 60637, USA.
Center for Research Informatics, The University of Chicago, Chicago, IL 60637, USA.
Genes (Basel). 2024 Feb 27;15(3):302. doi: 10.3390/genes15030302.
The carotid body (CB), located bilaterally at the carotid artery bifurcations, is the primary sensory organ for monitoring arterial blood O 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 gene-set enrichment analysis (GSEA). Analysis of RNA-Seq data showed 2604 DEGs of the total 12,696 genes shared between neonates and adults. Of the 2604 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 CBs compared to adult CBs, suggesting a possible link to differential developmental hypoxic responses seen in CB. Genes related to cytokine signaling (INFγ and TNFα) and transcription factors (CREB and NFΚB) mediated pathways were enriched in adult CBs, suggesting that 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 valuable insight into CB hypoxic sensing responses related to the development process.
颈动脉体(CB)位于颈动脉分叉处的两侧,是监测动脉血氧水平的主要感觉器官。CB 在出生时尚未成熟,对缺氧的敏感性较低,并且在新生儿生命的头几周内随着成熟而变得更加敏感。为了了解 CB 出生后缺氧反应的分子基础,我们从 5 天和 21 天大的 Sprague-Dawley 大鼠中分离出 CB,并进行了 RNA 测序,这允许对基因表达进行全面分析。使用 EdgeR 生成差异表达基因(DEGs),而使用基因集富集分析(GSEA)进行功能富集分析。RNA-Seq 数据分析显示,新生儿和成人之间共有 12696 个基因中的 2604 个 DEGs。在 2604 个 DEGs 中,有 924 个基因上调,1680 个基因下调。进一步分析表明,与氧化磷酸化(Ox/phos)和缺氧信号通路相关的基因在新生儿 CB 中明显上调,与 CB 中所见的差异发育性缺氧反应可能有关。与细胞因子信号(INFγ和 TNFα)和转录因子(CREB 和 NFΚB)介导的途径相关的基因在成人 CB 中富集,表明这些途径的表达可能与发育调控有关。通过 qRT-PCR 分析选定基因的 mRNA 变化验证了 RNA-Seq 结果。我们对生物途径的富集分析结果为 CB 与发育过程相关的缺氧感应反应提供了有价值的见解。