A temporal cortex cell atlas highlights gene expression dynamics during human brain maturation [Spatial Transcriptomics]

The human brain undergoes protracted post-natal maturation, guided by dynamic changes in gene expression. Most studies exploring these processes have used bulk tissue analyses, which mask cell type-specific gene expression dynamics. Here, using single nucleus (sn)RNA-seq on temporal lobe tissue, including samples of African ancestry, we build a joint paediatric and adult atlas of 75 cell subtypes, which we verify with spatial transcriptomics. We explore the differences between paediatric and adult cell subtypes, revealing the genes and pathways that change during brain maturation. Our results highlight excitatory neuron subtypes, including the LTK and FREM subtypes, that show elevated expression of genes associated with cognition and synaptic plasticity in paediatric tissue. The resources we present here improve our understanding of the brain during its development and contribute to global efforts to build an inclusive brain cell map. Overall design: Donated ante-mortem temporal coretx tissue samples from paediatric and adult patients were analysed using the 10x Genomics Visium spatial transcriptomics protocol

人类大脑在产后会经历漫长的成熟过程，该过程由基因表达的动态变化所驱动。既往针对该过程开展的多数研究采用大块组织（bulk tissue）分析方法，但这类手段会掩盖细胞类型特异性的基因表达动态变化。
本研究针对包含非洲血统样本的颞叶组织，采用单细胞核（single nucleus, sn）RNA测序（snRNA-seq）技术，构建了覆盖儿科与成人阶段的75种细胞亚型联合图谱，并通过空间转录组学（spatial transcriptomics）对该图谱进行验证。我们对比了儿科与成人细胞亚型之间的表达差异，揭示了大脑成熟过程中发生改变的基因与信号通路。研究结果凸显了LTK、FREM等兴奋性神经元亚型，它们在儿科脑组织中呈现出与认知及突触可塑性相关基因的高表达特征。
本研究提供的相关资源有助于加深我们对大脑发育过程的理解，并为全球范围内构建包容性大脑细胞图谱的合作项目贡献力量。
整体实验设计：本研究对来自儿科与成人患者的捐献生前颞叶皮层组织样本，采用10x Genomics Visium空间转录组学方案进行分析。