Astrocyte-enriched pan-brain aging transcriptome

Normal brain aging is marked by a cognitive decline, spurred by changes in cellular metabolism and homeostatic dysregulation, as well as modifications in synapses and neuronal connectivity. Astrocytes are well positioned as an effector of these changes, although how properties of astrocytes change with age remains unclear. Here, we address this question by profiling astrocytic gene expression from multiple brain regions of adult (4 month-old) and aged (2 years-old) mice. We isolated mRNA from transgenic mice where ribosomes within astrocytes were genetically tagged (GFAP-cre x RPL22-HA, astrocyte ribotag). We then used RNA sequencing to identify and quantify the astrocyte-enriched mRNA, analyzing 4 different brain regions: visual cortex, somatomotor cortex, hypothalamus, and cerebellum. Overall, we find that astrocyte expression of inflammatory and immune response factors increase with age, as well as changes in genes associated with metabolism, cholesterol synthesis, and synaptogenesis. Going forward, these data contribute to an understanding of astrocyte diversity and provide insight into the role of astrocytes in normal aging. Profile of aging and adult astrocyte-enriched mRNA from 4 different brain regions from GFAP-Ribotag mice (ribosomal pulldown), with 3 biological replicates and 1 input (non-pulldown) sample per time point and region

正常大脑衰老以认知功能衰退为典型特征，其发生由细胞代谢改变、稳态失衡，以及突触与神经元连接的修饰变化共同驱动。星形胶质细胞（Astrocytes）是介导此类变化的关键效应细胞，但其特性随衰老进程发生改变的具体机制仍有待阐明。本研究通过分析成年（4月龄）与衰老（24月龄）小鼠多个脑区域的星形胶质细胞基因表达谱，对这一科学问题展开探究。我们采用经基因改造的小鼠模型分离mRNA，该模型的星形胶质细胞核糖体已通过遗传方式标记（GFAP-cre x RPL22-HA，星形胶质细胞核糖体标签（astrocyte ribotag））。随后通过RNA测序（RNA sequencing）技术鉴定并定量星形胶质细胞富集的mRNA，共分析4个不同脑区域：视觉皮层、躯体运动皮层、下丘脑与小脑。整体而言，本研究发现星形胶质细胞中炎症与免疫应答相关因子的表达水平随衰老进程显著上调，同时与代谢、胆固醇合成及突触发生相关的基因表达也发生明显改变。本数据集将有助于解析星形胶质细胞的细胞多样性，并为阐明星形胶质细胞在正常大脑衰老过程中的作用提供关键研究依据。本数据集包含GFAP-核糖体标签（GFAP-Ribotag）小鼠4个不同脑区域的成年与衰老星形胶质细胞富集mRNA谱（基于核糖体下拉（ribosomal pulldown）技术），每个时间点与脑区域均设置3个生物学重复样本与1个输入（非下拉）对照样本。