Single-nucleus and single-cell transcriptomes compared in matched cortical cell types

被引:349
作者
Bakken, Trygve E. [1 ]
Hodge, Rebecca D. [1 ]
Miller, Jeremy A. [1 ]
Yao, Zizhen [1 ]
Thuc Nghi Nguyen [1 ]
Aevermann, Brian [2 ]
Barkan, Eliza [1 ]
Bertagnolli, Darren [1 ]
Casper, Tamara [1 ]
Dee, Nick [1 ]
Garren, Emma [1 ]
Goldy, Jeff [1 ]
Graybuck, Lucas T. [1 ]
Kroll, Matthew [1 ]
Lasken, Roger S. [2 ]
Lathia, Kanan [1 ]
Parry, Sheana [1 ]
Rimorin, Christine [1 ]
Scheuermann, Richard H. [2 ]
Schork, Nicholas J. [2 ]
Shehata, Soraya I. [1 ]
Tieu, Michael [1 ]
Phillips, John W. [1 ]
Bernard, Amy [1 ]
Smith, Kimberly A. [1 ]
Zeng, Hongkui [1 ]
Lein, Ed S. [1 ]
Tasic, Bosiljka [1 ]
机构
[1] Allen Inst Brain Sci, Seattle, WA 98109 USA
[2] J Craig Venter Inst, La Jolla, CA USA
关键词
RNA-SEQ; DIVERSITY; MOUSE; CLASSIFICATION; RETENTION; SUITE;
D O I
10.1371/journal.pone.0209648
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
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Transcriptomic profiling of complex tissues by single-nucleus RNA-sequencing (snRNA-seq) affords some advantages over single-cell RNA-sequencing (scRNA-seq). snRNA-seq provides less biased cellular coverage, does not appear to suffer cell isolation-based transcriptional artifacts, and can be applied to archived frozen specimens. We used well-matched snRNA-seq and scRNA-seq datasets from mouse visual cortex to compare cell type detection. Although more transcripts are detected in individual whole cells (similar to 11,000 genes) than nuclei (similar to 7,000 genes), we demonstrate that closely related neuronal cell types can be similarly discriminated with both methods if intronic sequences are included in snRNA-seq analysis. We estimate that the nuclear proportion of total cellular mRNA varies from 20% to over 50% for large and small pyramidal neurons, respectively. Together, these results illustrate the high information content of nuclear RNA for characterization of cellular diversity in brain tissues.
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页数:24
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