A human cell atlas of fetal chromatin accessibility

被引：249

作者：

Domcke, Silvia ^{[1
]}

Hill, Andrew J. ^{[1
]}

Daza, Riza M. ^{[1
]}

Cao, Junyue ^{[1
]}

O'Day, Diana R. ^{[2
]}

Pliner, Hannah A. ^{[3
]}

Aldinger, Kimberly A. ^{[2
,4
]}

Pokholok, Dmitry ^{[5
]}

Zhang, Fan ^{[5
]}

Milbank, Jennifer H. ^{[1
]}

Zager, Michael A. ^{[3
,6
]}

Glass, Ian A. ^{[2
,3
,4
]}

Steemers, Frank J. ^{[5
]}

Doherty, Dan ^{[2
,3
,4
]}

Trapnell, Cole ^{[1
,3
,7
]}

Cusanovich, Darren A. ^{[1
,8
,9
]}

Shendure, Jay ^{[1
,3
,7
,10
]}

机构：

[1] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA

[2] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA

[3] Brotman Baty Inst Precis Med, Seattle, WA 98195 USA

[4] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA USA

[5] Illumina, San Diego, CA USA

[6] Fred Hutchinson Canc Res Ctr, Ctr Data Visualizat, 1124 Columbia St, Seattle, WA 98104 USA

[7] Allen Discovery Ctr Cell Lineage Tracing, Seattle, WA 98104 USA

[8] Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ 85721 USA

[9] Univ Arizona, Asthma & Airway Dis Res Ctr, Tucson, AZ 85721 USA

[10] Howard Hughes Med Inst, Seattle, WA 98195 USA

来源：

SCIENCE | 2020年 / 370卷 / 6518期

关键词：

GENOME-WIDE ASSOCIATION; TRANSCRIPTION-FACTOR; DNA ELEMENTS; READ ALIGNMENT; BINDING SITES; IN-VIVO; GENERATION; ENCYCLOPEDIA; PROTEIN; GENES;

D O I：

10.1126/science.aba7612

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 chromatin landscape underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of chromatin accessibility and gene expression in fetal tissues. For chromatin accessibility, we devised a three-level combinatorial indexing assay and applied it to 53 samples representing 15 organs, profiling similar to 800,000 single cells. We leveraged cell types defined by gene expression to annotate these data and cataloged hundreds of thousands of candidate regulatory elements that exhibit cell type-specific chromatin accessibility. We investigated the properties of lineage-specific transcription factors (such as POU2F1 in neurons), organ-specific specializations of broadly distributed cell types (such as blood and endothelial), and cell type-specific enrichments of complex trait heritability. These data represent a rich resource for the exploration of in vivo human gene regulation in diverse tissues and cell types.

引用

页码：809 / +

页数：81

共 122 条

[1] Twist-1 Enhances Bone Marrow Mesenchymal Stromal Cell Support of Hematopoiesis by Modulating CXCL12 Expression [J].