CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Sci Rep. 2017 Jun 23;7(1):4121. doi: 10.1038/s41598-017-04356-7.
The functions of human brains highly depend on the precise temporal regulation of gene expression, and the temporal brain transcriptome profile across lifespan has been observed. The substantial transcriptome alteration in neural disorders like autism has also been observed and is thought to be important for the pathology. While the cell type composition is known to be variable in brains, it remains unclear how it contributes to the temporal and pathological transcriptome changes in brains. Here, we applied a transcriptome deconvolution procedure to an age series RNA-seq dataset of healthy and autism samples, to quantify the contribution of cell type composition in shaping the temporal and autism pathological transcriptome in human brains. We estimated that composition change was the primary factor of both types of transcriptome changes. On the other hand, genes with substantial composition-independent expression changes were also observed in both cases. Those temporal and autism pathological composition-independent changes, many of which are related to synaptic functions, indicate the important intracellular regulatory changes in human brains in both processes.
人类大脑的功能高度依赖于基因表达的精确时间调控，并且已经观察到了整个生命周期中大脑转录组的时间图谱。在自闭症等神经疾病中也观察到了大量的转录组改变，并且被认为对病理学很重要。虽然已知大脑中的细胞类型组成是可变的，但尚不清楚它如何导致大脑中时间和病理转录组的变化。在这里，我们将转录组去卷积程序应用于健康和自闭症样本的年龄序列 RNA-seq 数据集，以量化细胞类型组成在塑造人类大脑中时间和自闭症病理转录组中的贡献。我们估计组成变化是这两种转录组变化的主要因素。另一方面，在这两种情况下，也观察到了大量与组成无关的表达变化的基因。这些与时间相关的和自闭症病理的组成无关的变化，其中许多与突触功能有关，表明在这两个过程中人类大脑内部的重要调节变化。
