人类大脑单细胞 RNA 测序揭示的神经元亚型和多样性。
Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain.
机构信息
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
出版信息
Science. 2016 Jun 24;352(6293):1586-90. doi: 10.1126/science.aaf1204.
Abstract
The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture. These data demonstrate a robust and scalable method for identifying and categorizing single nuclear transcriptomes, revealing shared genes sufficient to distinguish previously unknown and orthologous neuronal subtypes as well as regional identity and transcriptomic heterogeneity within the human brain.
摘要
人类大脑具有极其复杂的细胞多样性和连接性，这些对我们的神经功能至关重要，但由于难以检测单个神经元，我们对其潜在的转录图谱的理解受到了阻碍。我们开发了一种可扩展的方法，用于对死后大脑中分离的神经元核中的 RNA 分子进行测序和定量，从大脑皮质的六个不同区域生成了 3227 组单细胞数据。使用迭代聚类和分类方法，我们鉴定了 16 种神经元亚型，然后根据已知标记和皮质细胞构筑进一步注释这些亚型。这些数据证明了一种用于识别和分类单个核转录组的强大且可扩展的方法，揭示了足以区分以前未知的和同源神经元亚型以及人类大脑内的区域身份和转录组异质性的共享基因。
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