A Single-Cell Atlas of In Vivo Mammalian Chromatin Accessibility

被引:497
作者
Cusanovich, Darren A. [1 ]
Hill, Andrew J. [1 ]
Aghamirzaie, Delasa [1 ]
Daza, Riza M. [1 ]
Pliner, Hannah A. [1 ]
Berletch, Joel B. [2 ]
Filippova, Galina N. [2 ]
Huang, Xingfan [1 ,3 ]
Christiansen, Lena [4 ]
DeWitt, William S. [1 ]
Lee, Choli [1 ]
Regalado, Samuel G. [1 ]
Read, David F. [1 ]
Steemers, Frank J. [4 ]
Disteche, Christine M. [2 ]
Trapnell, Cole [1 ,5 ]
Shendure, Jay [1 ,5 ,6 ]
机构
[1] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
[2] Univ Washington, Dept Pathol, Seattle, WA 98195 USA
[3] Univ Washington, Dept Comp Sci, Seattle, WA 98195 USA
[4] Illumina, San Diego, CA 92122 USA
[5] Brotman Baty Inst Precis Med, Seattle, WA 98195 USA
[6] Howard Hughes Med Inst, Seattle, WA 98195 USA
关键词
GENOME-WIDE ASSOCIATION; NEURONAL SUBTYPES; GENE-EXPRESSION; SEQUENCING DATA; READ ALIGNMENT; ANNOTATION; INFORMATION; GENERATION; LANDSCAPES; PHENOTYPE;
D O I
10.1016/j.cell.2018.06.052
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We applied a combinatorial indexing assay, sci-ATAC-seq, to profile genome-wide chromatin accessibility in similar to 100,000 single cells from 13 adult mouse tissues. We identify 85 distinct patterns of chromatin accessibility, most of which can be assigned to cell types, and similar to 400,000 differentially accessible elements. We use these data to link regulatory elements to their target genes, to define the transcription factor grammar specifying each cell type, and to discover in vivo correlates of heterogeneity in accessibility within cell types. We develop a technique for mapping single cell gene expression data to single-cell chromatin accessibility data, facilitating the comparison of atlases. By intersecting mouse chromatin accessibility with human genome-wide association summary statistics, we identify cell-type-specific enrichments of the heritability signal for hundreds of complex traits. These data define the in vivo landscape of the regulatory genome for common mammalian cell types at single-cell resolution.
引用
收藏
页码:1309 / +
页数:34
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