Single cell sequencing of astrocytes in the APP NL-F and APP PS1 models of ß-amyloidopathy

Bulk RNA-sequencing of astrocytes in the APP NL-F and APP PS1 models of ß-amyloidopathy, in which aspects of AD-related pathology progress at different speed, shows age-dependent gene expression changes. However, bulk RNA-seq does not provide insight into the heterogeneity of expression within this cell type, particularly relevant for such models, where reactive astrogliosis is most prominent in the vicinity of plaques. To investigate astrocyte heterogeneity in ß-amyloidopathy models, we thus performed single cell RNA-sequencing on astrocytes separated by FACS.

针对β-淀粉样蛋白病（β-amyloidopathy）的APP NL-F与APP PS1模型中的星形胶质细胞开展批量RNA测序（Bulk RNA-sequencing）后发现，此类模型的阿尔茨海默病（AD）相关病理进程速率存在差异，且呈现年龄依赖性的基因表达变化。然而，批量RNA测序无法揭示该细胞类型内的表达异质性，而这一点在这类模型中尤为关键——此类模型中反应性星形胶质细胞增生（reactive astrogliosis）在斑块附近最为显著。为探究β-淀粉样蛋白病模型中的星形胶质细胞异质性，我们通过荧光激活细胞分选（FACS）分离星形胶质细胞并实施了单细胞RNA测序（single cell RNA-sequencing）。