Global transcriptomic changes in aged mouse kidney podocytes

Like many cell types, the mechanisms and pathways underlying healthy aged-related changes to podocytes are not fully understood. Candidate pathways include oxidative stress, epigenetic changes, senescence, sirtuins, reduced autophagy and increased apoptosis, although detailed mechanisms underlying each pathway is not well defined. While detailed gene analysis has been undertaken on whole portions of the aging kidney, transcriptomic changes specific to podocytes in the aged kidney are not known. To address this, we used an inducible podocyte specific reporter mouse in which a cohort of podocytes are permanently labeled over the life time of the animal. RNA-seq was then used to measure transcriptional changes in genes in labeled podocytes in mice with advanced age, compared to podocytes from a cohort of young reporter mice. We did RNA-seq of aged and young podocytes from male and female mice. Aged female: 5 biological replicates; young female: 4 replicates; aged male: 3 replicates; young male: 4 replicates

与众多细胞类型类似，足细胞（podocytes）健康衰老相关变化背后的机制与通路尚未完全阐明。候选通路包括氧化应激、表观遗传改变、细胞衰老、沉默信息调节因子（sirtuins）、自噬水平降低以及凋亡水平升高，不过各通路背后的具体机制仍未得到清晰阐释。尽管已有针对衰老肾脏整体组织的详细基因分析，但衰老肾脏中足细胞特异性的转录组变化仍未明确。为解决这一问题，我们使用了诱导型足细胞特异性报告基因小鼠模型，该模型可在小鼠生命周期内对一组足细胞进行永久标记。随后，我们通过RNA测序（RNA-seq）检测了高龄小鼠标记足细胞的基因转录变化，并以年轻报告基因小鼠的足细胞作为对照。我们对雌雄小鼠的年轻与衰老足细胞均进行了RNA测序：衰老雌性小鼠组设置5个生物学重复，年轻雌性小鼠组设置4个生物学重复，衰老雄性小鼠组设置3个生物学重复，年轻雄性小鼠组设置4个生物学重复。