Spatial dynamics of brain development and neuroinflammation [Epigenomic_data]

Spatially mapping multiple omics layers across time enables dissection of mechanisms underlying brain development, differentiation, arealization, and disease. Here, we deploy spatial tri-omics to chart spatiotemporal remodeling in development and neuroinflammation. We generate a tri-omic atlas of mouse brain from postnatal day P0–P21 and compare corresponding regions in developing human brain. In cortex, a subset of layer-defining transcription factors shows temporally persistent and spatially spreading chromatin accessibility. In corpus callosum, myelin genes exhibit dynamic chromatin priming across subregions, and layer-specific projection neurons appear to coordinate axonogenesis and myelination. In a lysolecithin (LPC) model, we observe molecular programs shared between development and neuroinflammation. Microglia display conserved and distinct inflammatory and resolution programs and are transiently activated both at lesion cores and at distal sites, presumably via neuronal circuitry. These data reveal common and divergent mechanisms and provide a resource for studying brain development, function, and disease. Overall design: Samples consist of mouse brain tissue sections collected across normal postnatal development (P0, P2, P5, P7, P10, P21) as well as from a lysolecithin (LPC)-induced demyelination model at multiple recovery stages (5, 10, 21 days post-lesion). Each sample was processed for spatial multi-omic profiling using DBiT-seq. Biological replicates are included for each developmental stage and lesion condition. Experimental variables under investigation include developmental timepoint, brain region, and lesion status (lesion core, distal white matter, and control). These samples enable comparative analyses of spatiotemporal dynamics in brain development and demyelination.

时空多组学图谱绘制可解析脑发育、分化、区域特化及疾病发生的潜在机制。本研究采用空间三组学（spatial tri-omics）技术，绘制发育与神经炎症过程中的时空重塑图谱。我们构建了出生后第0天（P0）至第21天（P21）小鼠脑的三组学图谱，并与发育中人脑的对应区域开展比对分析。在大脑皮层中，部分层特异性转录因子展现出随时间持续存在且空间上扩散的染色质可及性特征。在胼胝体中，髓鞘相关基因在各亚区域呈现动态的染色质预激活状态，且层特异性投射神经元似乎协同调控轴突发生与髓鞘形成。在溶血卵磷脂（lysolecithin, LPC）诱导的脱髓鞘模型中，我们观测到发育进程与神经炎症共享的分子程序。小胶质细胞展现出保守且独特的炎症与炎症消退程序，并在损伤核心区及远端区域出现暂时性激活，推测该过程通过神经元环路介导。本研究揭示了脑生理与病理过程中的共通与差异化机制，为脑发育、功能及疾病研究提供了珍贵的数据集资源。

实验设计概述：本次研究的样本涵盖正常出生后发育阶段（P0、P2、P5、P7、P10、P21）的小鼠脑组织切片，以及溶血卵磷脂（LPC）诱导的脱髓鞘模型在多个恢复阶段（损伤后5、10、21天）的脑组织样本。所有样本均采用DBiT-seq技术进行空间多组学分析。每个发育阶段与损伤处理组均设置生物学重复。本研究考察的实验变量包括发育时间点、脑区域以及损伤状态（损伤核心区、远端白质与对照组）。上述样本可用于脑发育与脱髓鞘过程中的时空动态特征比较分析。