Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.
Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
Neuron. 2022 Feb 2;110(3):452-469.e14. doi: 10.1016/j.neuron.2021.10.036. Epub 2021 Nov 18.
The hippocampal-entorhinal system supports cognitive functions, has lifelong neurogenic capabilities in many species, and is selectively vulnerable to Alzheimer's disease. To investigate neurogenic potential and cellular diversity, we profiled single-nucleus transcriptomes in five hippocampal-entorhinal subregions in humans, macaques, and pigs. Integrated cross-species analysis revealed robust transcriptomic and histologic signatures of neurogenesis in the adult mouse, pig, and macaque but not humans. Doublecortin (DCX), a widely accepted marker of newly generated granule cells, was detected in diverse human neurons, but it did not define immature neuron populations. To explore species differences in cellular diversity and implications for disease, we characterized subregion-specific, transcriptomically defined cell types and transitional changes from the three-layered archicortex to the six-layered neocortex. Notably, METTL7B defined subregion-specific excitatory neurons and astrocytes in primates, associated with endoplasmic reticulum and lipid droplet proteins, including Alzheimer's disease-related proteins. This resource reveals cell-type- and species-specific properties shaping hippocampal-entorhinal neurogenesis and function.
海马-内嗅系统支持认知功能,在许多物种中具有终身神经发生能力,并且易受阿尔茨海默病的影响。为了研究神经发生潜力和细胞多样性,我们对人类、猕猴和猪的五个海马-内嗅亚区的单个核转录组进行了分析。跨物种综合分析显示,成年小鼠、猪和猕猴具有强大的神经发生转录组和组织学特征,但人类没有。双皮质素 (DCX) 是一种广泛接受的新生成颗粒细胞标志物,在多种人类神经元中被检测到,但它不能定义未成熟神经元群体。为了探索细胞多样性的物种差异及其对疾病的影响,我们对特定于亚区的、转录定义的细胞类型以及从三层旧皮质到六层新皮质的过渡变化进行了表征。值得注意的是,METTL7B 在灵长类动物中定义了特定于亚区的兴奋性神经元和星形胶质细胞,与内质网和脂滴蛋白有关,包括与阿尔茨海默病相关的蛋白质。该资源揭示了塑造海马-内嗅神经发生和功能的细胞类型和物种特异性特性。