RNA sequencing of Tau overexpressing human SH-SY5Y cell line revels that Tau protein is able to alter global gene expression and chromatin structure. RNA sequencing of Tau overexpressing human SH-SY5Y cell line revels that Tau protein is able to alter global gene expression and chromatin structure

Alzheimer’s disease and tauopathies are neurodegenerative disorders characterized by the alteration of neuronal homeostasis and aggregation of Tau protein. Tau is generally considered a protein involved in cytoskeletal stability and transport whose destabilization leads to neuronal dysfunction and death. Despite the knowledge about canonical roles of Tau, in recent years it has been observed that Tau is a key player in several neuronal functions. We previously described that Tau destabilization and nuclear delocalization alters the expression of glutamatergic genes mediating early neuronal damage. In this paper we propose that Tau is able to deeply affect the neuronal transcriptome and that its availability is associated to gene expression alterations occurring in developing intermediate AD phases. In addition, we identify the epigenetic pathway as strongly altered by Tau during AD progression. Overall design: Differential gene expression analysis of RNA-seq data performed on SH-SY5Y cells overexpressing Tau 0N4R isoform (SH_tau) or a control vector (SH_ctrl). 6 samples in total: 3 samples SH-SY5Y overexpressing Tau 0N4R; 3 samples SH-SY5Y expressing control vector.

阿尔茨海默病（Alzheimer’s disease）与tau蛋白病（tauopathies）均为以神经元稳态失衡及Tau蛋白（Tau protein）聚集为特征的神经退行性疾病。Tau蛋白通常被认为是参与细胞骨架稳定与物质转运的蛋白，其稳定性遭到破坏会引发神经元功能障碍与死亡。尽管学界对Tau的经典功能已有一定认知，但近年来研究发现，Tau在多种神经元生理过程中均发挥关键调控作用。我们此前的研究表明，Tau的稳定性丧失及细胞核错位会改变介导早期神经元损伤的谷氨酸能基因的表达。本研究提出，Tau可深刻影响神经元转录组，且其蛋白水平与阿尔茨海默病进展中期出现的基因表达异常密切相关。此外，我们还鉴定出在阿尔茨海默病病程中受Tau显著调控的表观遗传通路。整体实验设计：本研究对过表达Tau 0N4R亚型的SH-SY5Y细胞（记为SH_tau组）及转染空载体的对照组细胞（SH_ctrl组）的RNA测序（RNA-seq）数据进行差异基因表达分析。共纳入6个样本：3份过表达Tau 0N4R的SH-SY5Y细胞样本，3份转染空载体的SH-SY5Y细胞样本。