Spatial transcriptomics map of the embryonic mouse brain: a tool to explore neurogenesis

The developing brain has a complex and well-organized anatomical structure comprising different types of neural and non-neural cells. Stem cells, progenitors, and newborn neurons tightly interact with their neighbouring cells and tissue microenvironment, and this intricate interplay ultimately shapes the output of neurogenesis. Given the relevance of spatial cues during brain development, we acknowledge the necessity for a transcriptomics atlas within the tissue context accessible to the neurodevelopmental community. To fulfil this need, we offer an open-access spatial gene expression browser of the embryonic mouse brain at the peak of neurogenesis. Using 10x Visium technology, we generated spatially-resolved RNAseq data from E13.5 embryonic brain sections. Unsupervised clustering reliably defined specific cell type populations of diverse lineages and maturational states. Differential expression analysis revealed unique transcriptional signatures across specific embryonic brain areas, uncovering novel features inherent to particular anatomical domains. Furthermore, we integrated single-cell RNAseq data from E13.5 mouse brains into our Spatial Transcriptomics data, adding tissue context to single-cell resolution. In summary, we provide a valuable tool that enables the exploration and discovery of unforeseen molecular players involved in neurogenesis, particularly in the crosstalk between different cell types. Four sections from four different WT mouse embryonic heads (stage E13.5) were extracted for spatial transcriptomics using the 10x Genomics Visium platform in order to identify areas of the embryonic brain with different cell lineages and maturation states at the peak of neurogenesis.发育中的大脑拥有复杂且高度有序的解剖结构，由多种神经细胞与非神经细胞共同构成。干细胞、祖细胞以及新生神经元与其邻近细胞和组织微环境之间存在紧密的相互作用，这种复杂的互作最终决定了神经发生的最终结果。鉴于大脑发育过程中空间线索的重要性，我们认为神经发育研究领域亟需组织原位语境下的转录组图谱资源。为满足这一需求，我们构建了面向神经发生高峰期胚胎小鼠大脑的开放获取空间基因表达浏览器。本研究借助10x Visium技术，对E13.5（胚胎发育第13.5天）的胚胎大脑切片进行了空间分辨转录组测序，获取了相关数据。通过无监督聚类分析，我们可靠地鉴定出了不同细胞谱系与成熟状态的特异性细胞类群。差异表达分析揭示了特定胚胎大脑区域的独特转录特征，同时发掘出特定解剖区域固有的全新生物学特性。此外，我们将E13.5小鼠大脑的单细胞RNA测序数据与本研究的空间转录组数据进行整合，为单细胞分辨率数据赋予了组织原位语境信息。综上，本研究提供了一款极具价值的研究工具，可用于探索并发掘神经发生过程中（尤其是不同细胞类型间互作过程中）尚未被发现的关键分子调控因子。本研究使用10x Genomics Visium平台，对4只不同野生型（Wild Type, WT）E13.5阶段小鼠胚胎头部的4个切片进行空间转录组测序，以鉴定神经发生高峰期胚胎大脑中具有不同细胞谱系与成熟状态的区域。