Differential gene expression between cortex and striatum of WT and ASCT1 (Slc1a4)-knockout mice

In order to explore possible consequence of ASCT1 (Slc1a4) deletion in neurodevelopment, we carried out RNA sequencing of the striatum, which was altered in MRI analysis, and compared with the neocortex, which was unaffected. We found significant changes in 375 transcripts in the striatum of adult mice at adjusted p values lower than 0.05. No changes in gene expression were observed in the neocortex. Enrichment analysis using non-redundant reciprocal linkage of genes identified 11 metagroups, with overrepresentation of genes linked to axonal guidance and neurodevelopmental processes in the striatum. The most significant changes were seen in axon guidance genes, suggesting changes in neurodevelopmental-related gene transcripts in ASCT1-KO mice, compatible with the findings in human familial ASCT1 mutations. We generated RNAseq data from the cerebral cortex and striatum of Wild Type and ASCT1-KO mice on Illumina NextSeq500, 75 bp single-end reads, high-output mode (Illumina, FC-404-2005).为探究ASCT1（Slc1a4）敲除对神经发育的潜在影响，我们对磁共振成像（Magnetic Resonance Imaging, MRI）分析显示存在异常的纹状体开展RNA测序，并与未受影响的新皮层进行对照。我们在成年小鼠的纹状体中发现，经多重检验校正后的p值低于0.05的375个转录本存在显著表达差异；新皮层中未观测到任何基因表达变化。通过非冗余基因反向关联分析开展富集分析，共鉴定出11个基因元簇，其中纹状体中与轴突导向及神经发育过程相关的基因呈现显著富集。其中轴突导向相关基因的表达变化最为显著，提示ASCT1敲除（ASCT1 knockout, ASCT1-KO）小鼠的神经发育相关基因转录本发生了改变，这与人类家族性ASCT1突变的相关研究结果相符。我们利用Illumina NextSeq500测序平台，采用75 bp单端读取、高通量输出模式（Illumina, FC-404-2005），获取了野生型（Wild Type, WT）与ASCT1敲除小鼠的大脑皮层及纹状体的RNA测序数据。