Abstract:
Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangling the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq and spatial transcriptomics of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their inherent transcriptional structure in the human dorsal striatum. We propose a comprehensive taxonomy of striatal interneurons with eight main classes and fourteen subclasses, providing their full transcriptomic identity and spatial expression profile as well as additional quantitative FISH validation for specific populations. We have also delineated the correspondence of our taxonomy with previous standardized classifications and shown the main transcriptomic and class abundance differences between caudate nucleus and putamen. Notably, based on key functional genes such as ion channels and synaptic receptors, we found matching known mouse interneuron populations for the most abundant populations, the recently described PTHLH and TAC3 interneurons. Finally, we were able to integrate other published datasets with ours, supporting the generalizability of this harmonized taxonomy.
摘要:
破译纹状体中间神经元多样性是了解基底神经节回路和解开影响这种大脑结构的复杂神经和精神疾病的关键。我们对死后的人尾状核和壳核样品进行了snRNA-seq和空间转录组学,以阐明人背纹状体中中间神经元种群的多样性和丰度及其固有的转录结构。我们提出了纹状体中间神经元的综合分类法,包括八个主类和十四个亚类,提供其完整的转录组身份和空间表达谱,以及针对特定群体的其他定量FISH验证。我们还描述了我们的分类法与以前的标准化分类的对应关系,并显示了尾状核和壳核之间的主要转录组和类别丰度差异。值得注意的是,基于离子通道和突触受体等关键功能基因,我们发现已知的小鼠中间神经元种群与最丰富的种群相匹配,最近描述的PTHLH和TAC3中间神经元。最后,我们能够将其他已发布的数据集与我们的数据集集成在一起,支持这种协调分类法的普遍性。