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
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
收藏
页码:809 / +
页数:81
相关论文
共 122 条
[101]   A single-cell survey of the human first-trimester placenta and decidua [J].
Suryawanshi, Hemant ;
Morozov, Pavel ;
Straus, Alexander ;
Sahasrabudhe, Nicole ;
Max, Klaas E. A. ;
Garzia, Aitor ;
Kustagi, Manjunath ;
Tuschl, Thomas ;
Williams, Zev .
SCIENCE ADVANCES, 2018, 4 (10)
[102]   GATA/Heme Multi-omics Reveals a Trace Metal-Dependent Cellular Differentiation Mechanism [J].
Tanimura, Nobuyuki ;
Liao, Ruiqi ;
Wilson, Gary M. ;
Dent, Matthew R. ;
Cao, Miao ;
Burstyn, Judith N. ;
Hematti, Peiman ;
Liu, Xin ;
Zhang, Yuannyu ;
Zheng, Ye ;
Keles, Sunduz ;
Xu, Jian ;
Coon, Joshua J. ;
Bresnick, Emery H. .
DEVELOPMENTAL CELL, 2018, 46 (05) :581-+
[103]   The octamer binding transcription factor Oct-1 is a stress sensor [J].
Tantin, D ;
Schild-Poulter, C ;
Wang, V ;
Haché, RJG ;
Sharp, PA .
CANCER RESEARCH, 2005, 65 (23) :10750-10758
[104]   HUMAN FOETAL HAEMATOPOIESIS .2. HEPATIC HAEMATOPOIESIS IN HUMAN FOETUS [J].
THOMAS, DB ;
YOFFEY, JM .
BRITISH JOURNAL OF HAEMATOLOGY, 1964, 10 (02) :193-&
[105]   Reelin and brain development [J].
Tissir, F ;
Goffinet, AM .
NATURE REVIEWS NEUROSCIENCE, 2003, 4 (06) :496-505
[106]   The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells [J].
Trapnell, Cole ;
Cacchiarelli, Davide ;
Grimsby, Jonna ;
Pokharel, Prapti ;
Li, Shuqiang ;
Morse, Michael ;
Lennon, Niall J. ;
Livak, Kenneth J. ;
Mikkelsen, Tarjei S. ;
Rinn, John L. .
NATURE BIOTECHNOLOGY, 2014, 32 (04) :381-U251
[107]   Population snapshots predict early haematopoietic and erythroid hierarchies [J].
Tusi, Betsabeh Khoramian ;
Wolock, Samuel L. ;
Weinreb, Caleb ;
Hwang, Yung ;
Hidalgo, Daniel ;
Zilionis, Rapolas ;
Waisman, Ari ;
Huh, Jun R. ;
Klein, Allon M. ;
Socolovsky, Merav .
NATURE, 2018, 555 (7694) :54-+
[108]   The Oct1 transcription factor and epithelial malignancies: Old protein learns new tricks [J].
Vazquez-Arreguin, Karina ;
Tantin, Dean .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2016, 1859 (06) :792-804
[109]   VISTA Enhancer Browser - a database of tissue-specific human enhancers [J].
Visel, Axel ;
Minovitsky, Simon ;
Dubchak, Inna ;
Pennacchio, Len A. .
NUCLEIC ACIDS RESEARCH, 2007, 35 :D88-D92
[110]  
Vitak SA, 2017, NAT METHODS, V14, P302, DOI [10.1038/NMETH.4154, 10.1038/nmeth.4154]