The inhibition of LSD1 via sequestration contributes to tau-mediated neurodegeneration

In this dataset, we evalute the effect of modulating the levels of LSD1 in the PS19 tauopathy mouse (mouse that expresses the P301S mutated form of the human tau transgene). First we reduced the levels of LSD1 by crossing PS19 Tau mice with mice heterozygous for Lsd1. This results in an exacerbation of the neurodegenerative phenotype as well as an increase in the transcripational changes observed in taupoathy mice. Secondy, we overexprssed LSD1 in neurons of the adult tauopathy mouse through viral injection direclty into the hippocampus. This resulted in a reduce of neuronal cell death as well as the associated transcriptional changes. RNA sequencing of the hippocampus of adult mice. First, samples 1-14 are 9 month old mice expressing the P301S mutated form of tau transgene with that are either wildtype or heterozygous of Lsd1. Wildtype and Lsd1 heterozgyous mice are used as controls. Second, for samples 15- 23, 11 month old mice expressing the P301S tau transgene injected with a neruonal specfic AAV virus directly into the hippocampus expressing either LSD1 or HA (control) virus. Wildtype mice injected with HA virus are used as controls.

本数据集旨在评估调控PS19 tau病小鼠（表达人类tau转基因P301S突变型的小鼠）体内组蛋白赖氨酸去甲基化酶1（LSD1）的水平所产生的生物学效应。实验分为两个部分：其一，通过将PS19 Tau小鼠与Lsd1杂合子小鼠杂交，下调LSD1的表达水平，该操作加剧了tau病小鼠的神经退行性表型，并增强了其观察到的转录组改变；其二，通过直接向成年tau病小鼠的海马体注射病毒载体，在其神经元中过表达LSD1，该处理减少了神经元细胞死亡，并缓解了相关的转录组改变。
本研究对成年小鼠的海马体组织开展了RNA测序，样本分组如下：
1. 样本1~14：均为9月龄、表达人类tau转基因P301S突变型的小鼠，分为Lsd1野生型与Lsd1杂合子亚组，其中Lsd1野生型与杂合子小鼠均作为对照。
2. 样本15~23：均为11月龄、表达人类tau转基因P301S突变型的小鼠，通过直接向海马体注射神经元特异性腺相关病毒（AAV），分别携带LSD1过表达序列或HA（血凝素）对照序列，其中注射HA病毒的野生型小鼠作为整体实验对照。