Transcriptional regulatory network of developing mouse telencephalon

In mouse, a vesicle forms at the anterior part of the developing embryo at 9.5 day/stage (M9.5), which further develops into telencephalon at M10.5 day/stage. The equivalent stages in chick embryo are referred to as HH17 and HH24. We sequenced RNA populations from telencephalic region at the early (M9.5 and HH17) and late stages (M10.5 and HH24) of mouse and chick embryo. Four samples were sequenced for each stage of telencephalon development. The resulting RNA sequencing reads were used to assemble transcripts and for counting their abundance. The read counts for each transcript then used to compute its differential expression between M9.5 and M10.5 stages in mouse. Likewise, each chick transcript was compared between H17 and HH24 stages.

Genes having significant p-values with positive log2 -fold change represent increased expression at developmental stage B (late) compared to stage A (early) and are referred to as up-regulated (UP). Likewise, genes with negative log2-fold change represent decreased expression at stage B compared to stage A and are referred to as down-regulated (Down, DN). Gene expression with p-values above 0.05 was considered non-significant and represents no change between stage B and stage A and is referred to as no change (NC). Genes with read count roughly less than five in less than four samples were considered not expressed and referred to as NE. These four groups of genes were further categorized into sixteen groups based on the expression status of mouse and chick gene orthologs. These sixteen gene groups; UP, DN, NC, and NE mouse gene groups; and a gene group composed of all differentially expressed genes in mouse (DEG), were submitted to iRegulon Cytoscape plugin for predicting their transcriptional regulatory factors.

These gene groups and iRegulon prediction results for each of the groups are provided as datasets. Using significant iRegulon prediction results, we reconstructed transcriptional regulatory network for mouse telencephalon development, which is also provided as network file. In addition to a single excel file containing results for some of the gene groups where we found meaningful connection between the predicted transcription factors and their differentially expressed targets genes.

在小鼠中，发育胚胎的前部会在9.5天/阶段（M9.5）形成囊泡，并于M10.5天/阶段进一步发育为端脑（telencephalon）。鸡胚中的对应发育阶段为HH17与HH24。我们对小鼠和鸡胚早期（M9.5与HH17）及晚期（M10.5与HH24）的端脑区域进行了RNA群体测序。端脑发育的每个阶段均设置4个测序样本。所得的RNA测序读段用于转录本组装与表达量定量。随后，基于各转录本的读段计数，计算小鼠M9.5与M10.5阶段间的差异表达水平；同理，对鸡胚HH17与HH24阶段的各转录本开展差异表达比较。

当基因的p值显著且log₂倍变化（log₂-fold change）为正时，代表其在发育晚期阶段B相较于早期阶段A的表达量上调，这类基因被称为上调基因（UP）；当log₂倍变化为负时，代表其在阶段B的表达量相较于阶段A下调，这类基因被称为下调基因（Down, DN）。若基因表达的p值大于0.05，则认为该表达变化无统计学显著性，即阶段A与阶段B间无表达差异，这类基因被称为无变化基因（NC）。若某基因在少于4个样本中的读段计数均小于5，则判定为未表达基因（NE）。基于小鼠与鸡胚基因的同源基因表达状态，上述4类基因可进一步划分为16个基因组。这16个基因组包括：小鼠的UP、DN、NC、NE基因组，以及包含小鼠所有差异表达基因（differentially expressed genes, DEG）的基因组。我们将这些基因组提交至iRegulon Cytoscape插件，以预测其转录调控因子。

本数据集包含上述16个基因组，以及每个基因组的iRegulon预测结果。基于具有统计学显著性的iRegulon预测结果，我们重构了小鼠端脑发育的转录调控网络，该网络文件也随数据集一同提供。此外，还附带一份Excel文件，收录了部分基因组的分析结果——其中我们发现了预测转录因子与其差异表达靶基因间存在明确的调控关联。