RNA sequencing of cortical neurons from Kat6b deficient mouse foetuses

The RNA sequencing data are part of a study reporting and investigating a mouse model of the Say-Barber-Biesecker-Young-Simpson (SBBYS) syndrome (OMIM:603736) and demonstrating proof-of-principle efficacy of postnatal treatment with sodium valproate (VPA) or acetyl-carnitine (ALCAR). The KAT6B gene encodes a histone lysine acetyltransferase. The RNA sequencing experiments identified genes that are differentially expressed between Vehicle treated Kat6b+/– and Kat6b+/+ cortical neurons and the subset genes that are restored to normal expression after treatment with ALCAR or VPA. Cortical neurons were isolated from four Kat6b+/– and four Kat6b+/+ E16.5 mouse cerebral cortex. Cells from each cortical neuron isolate were cultured with 1 mM ALCAR, 1 mM VPA or untreated medium (Vehicle) for 4 days. Overall design: There were n=4 mice of each genotype, Kat6b+/– (Dec/+) or Kat6b+/+ (wild type - WT). Neurons from each mice were subject to three treatments (ALCAR, VPA or vehicle). Each RNA library sample was sequenced twice (as identified by the date, 300823 or 080923 on the data files) to increase sequencing depth. These are pure technical replicates and were combined in the analysis. Differential analyses were performed indepently for the ALCAR/Vehicle and VPA/Vehicle sample groups, identifying differentially expressed genes between the various treatment/genotype group combinations.

本RNA测序数据隶属于一项研究，该研究旨在报道并探究赛伊-巴伯-比泽克-扬-辛普森综合征（Say-Barber-Biesecker-Young-Simpson syndrome, SBBYS，OMIM:603736）的小鼠模型，并验证丙戊酸钠（sodium valproate, VPA）与乙酰肉碱（acetyl-carnitine, ALCAR）产后治疗的概念验证性疗效。KAT6B基因编码一种组蛋白赖氨酸乙酰转移酶。本RNA测序实验筛选出了载体处理的Kat6b+/–与Kat6b+/+皮层神经元之间的差异表达基因，以及经ALCAR或VPA治疗后表达恢复至正常水平的基因子集。
实验所用皮层神经元分离自4只Kat6b+/–与4只Kat6b+/+的E16.5小鼠大脑皮层。将每一份皮层神经元分离物分别置于1 mM ALCAR、1 mM VPA或未处理培养基（载体对照，Vehicle）中培养4天。
实验设计详情如下：两种基因型小鼠各4只，分别为Kat6b+/–（即Dec/+）与Kat6b+/+（野生型，WT）。每只小鼠的神经元均接受三种处理：ALCAR、VPA或载体对照。每份RNA文库样本均进行两次测序（数据文件以日期300823或080923标识）以提升测序深度，此为纯技术重复，分析时将其合并。分别针对ALCAR/Vehicle与VPA/Vehicle样本组开展独立差异分析，以鉴定不同处理/基因型组合间的差异表达基因。