Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain

被引：633

作者：

Lake, Blue B. ^{[1
]}

Ai, Rizi ^{[2
]}

Kaeser, Gwendolyn E. ^{[3
,4
]}

Salathia, Neeraj S. ^{[5
]}

Yung, Yun C. ^{[3
]}

Liu, Rui ^{[1
]}

Wildberg, Andre ^{[2
]}

Gao, Derek ^{[1
]}

Fung, Ho-Lim ^{[1
]}

Chen, Song ^{[1
]}

Vijayaraghavan, Raakhee ^{[5
]}

Wong, Julian ^{[3
]}

Chen, Allison ^{[3
]}

Sheng, Xiaoyan ^{[3
]}

Kaper, Fiona ^{[5
]}

Shen, Richard ^{[5
]}

Ronaghi, Mostafa ^{[5
]}

Fan, Jian-Bing ^{[5
]}

Wang, Wei ^{[2
]}

Chun, Jerold ^{[3
]}

Zhang, Kun ^{[1
]}

机构：

[1] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[3] Scripps Res Inst, Dorris Neurosci Ctr, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA

[4] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA

[5] Illumina, San Diego, CA USA

来源：

SCIENCE | 2016年 / 352卷 / 6293期

关键词：

ADULT HUMAN BRAIN; TRANSCRIPTOME; CELLS; SEQ; SIGNATURES;

D O I：

10.1126/science.aaf1204

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1586 / 1590

页数：5

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