Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing

被引:799
作者
Cusanovich, Darren A. [1 ]
Daza, Riza [1 ]
Adey, Andrew [2 ]
Pliner, Hannah A. [1 ]
Christiansen, Lena [3 ]
Gunderson, Kevin L. [3 ]
Steemers, Frank J. [3 ]
Trapnell, Cole [1 ]
Shendure, Jay [1 ]
机构
[1] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
[2] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA
[3] Illumina Inc, Adv Res Grp, San Diego, CA USA
关键词
RNA-SEQ; HUMAN GENOME; IN-VITRO; TRANSPOSITION; CONTIGUITY; EXPRESSION; FATE;
D O I
10.1126/science.aab1601
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
Technical advances have enabled the collection of genome and transcriptome data sets with single-cell resolution. However, single-cell characterization of the epigenome has remained challenging. Furthermore, because cells must be physically separated before biochemical processing, conventional single-cell preparatory methods scale linearly. We applied combinatorial cellular indexing to measure chromatin accessibility in thousands of single cells per assay, circumventing the need for compartmentalization of individual cells. We report chromatin accessibility profiles from more than 15,000 single cells and use these data to cluster cells on the basis of chromatin accessibility landscapes. We identify modules of coordinately regulated chromatin accessibility at the level of single cells both between and within cell types, with a scalable method that may accelerate progress toward a human cell atlas.
引用
收藏
页码:910 / 914
页数:5
相关论文
共 22 条
[1]   In vitro, long-range sequence information for de novo genome assembly via transposase contiguity [J].
Adey, Andrew ;
Kitzman, Jacob O. ;
Burton, Joshua N. ;
Daza, Riza ;
Kumar, Akash ;
Christiansen, Lena ;
Ronaghi, Mostafa ;
Amini, Sasan ;
Gunderson, Kevin L. ;
Steemers, Frank J. ;
Shendure, Jay .
GENOME RESEARCH, 2014, 24 (12) :2041-2049
[2]   Rapid, low-input, low-bias construction of shotgun fragment libraries by high-density in vitro transposition [J].
Adey, Andrew ;
Morrison, Hilary G. ;
Asan ;
Xun, Xu ;
Kitzman, Jacob O. ;
Turner, Emily H. ;
Stackhouse, Bethany ;
MacKenzie, Alexandra P. ;
Caruccio, Nicholas C. ;
Zhang, Xiuqing ;
Shendure, Jay .
GENOME BIOLOGY, 2010, 11 (12)
[3]   Haplotype-resolved whole-genome sequencing by contiguity-preserving transposition and combinatorial indexing [J].
Amini, Sasan ;
Pushkarev, Dmitry ;
Christiansen, Lena ;
Kostem, Emrah ;
Royce, Tom ;
Turk, Casey ;
Pignatelli, Natasha ;
Adey, Andrew ;
Kitzman, Jacob O. ;
Vijayan, Kandaswamy ;
Ronaghi, Mostafa ;
Shendure, Jay ;
Gunderson, Kevin L. ;
Steemers, Frank J. .
NATURE GENETICS, 2014, 46 (12) :1343-1349
[4]   High-resolution mapping and characterization of open chromatin across the genome [J].
Boyle, Alan P. ;
Davis, Sean ;
Shulha, Hennady P. ;
Meltzer, Paul ;
Margulies, Elliott H. ;
Weng, Zhiping ;
Furey, Terrence S. ;
Crawford, Gregory E. .
CELL, 2008, 132 (02) :311-322
[5]  
Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/nmeth.2688, 10.1038/NMETH.2688]
[6]   Single-Cell RNA-Seq Reveals Dynamic, Random Monoallelic Gene Expression in Mammalian Cells [J].
Deng, Qiaolin ;
Ramskold, Daniel ;
Reinius, Bjorn ;
Sandberg, Rickard .
SCIENCE, 2014, 343 (6167) :193-196
[7]   An integrated encyclopedia of DNA elements in the human genome [J].
Dunham, Ian ;
Kundaje, Anshul ;
Aldred, Shelley F. ;
Collins, Patrick J. ;
Davis, CarrieA. ;
Doyle, Francis ;
Epstein, Charles B. ;
Frietze, Seth ;
Harrow, Jennifer ;
Kaul, Rajinder ;
Khatun, Jainab ;
Lajoie, Bryan R. ;
Landt, Stephen G. ;
Lee, Bum-Kyu ;
Pauli, Florencia ;
Rosenbloom, Kate R. ;
Sabo, Peter ;
Safi, Alexias ;
Sanyal, Amartya ;
Shoresh, Noam ;
Simon, Jeremy M. ;
Song, Lingyun ;
Trinklein, Nathan D. ;
Altshuler, Robert C. ;
Birney, Ewan ;
Brown, James B. ;
Cheng, Chao ;
Djebali, Sarah ;
Dong, Xianjun ;
Dunham, Ian ;
Ernst, Jason ;
Furey, Terrence S. ;
Gerstein, Mark ;
Giardine, Belinda ;
Greven, Melissa ;
Hardison, Ross C. ;
Harris, Robert S. ;
Herrero, Javier ;
Hoffman, Michael M. ;
Iyer, Sowmya ;
Kellis, Manolis ;
Khatun, Jainab ;
Kheradpour, Pouya ;
Kundaje, Anshul ;
Lassmann, Timo ;
Li, Qunhua ;
Lin, Xinying ;
Marinov, Georgi K. ;
Merkel, Angelika ;
Mortazavi, Ali .
NATURE, 2012, 489 (7414) :57-74
[8]   Combinatorial labeling of single cells for gene expression cytometry [J].
Fan, H. Christina ;
Fu, Glenn K. ;
Fodor, Stephen P. A. .
SCIENCE, 2015, 347 (6222)
[9]   Massively parallel polymerase cloning and genome sequencing of single cells using nanoliter microwells [J].
Gole, Jeff ;
Gore, Athurva ;
Richards, Andrew ;
Chiu, Yu-Jui ;
Fung, Ho-Lim ;
Bushman, Diane ;
Chiang, Hsin-I ;
Chun, Jerold ;
Lo, Yu-Hwa ;
Zhang, Kun .
NATURE BIOTECHNOLOGY, 2013, 31 (12) :1126-+
[10]   Massively Parallel Single-Cell RNA-Seq for Marker-Free Decomposition of Tissues into Cell Types [J].
Jaitin, Diego Adhemar ;
Kenigsberg, Ephraim ;
Keren-Shaul, Hadas ;
Elefant, Naama ;
Paul, Franziska ;
Zaretsky, Irina ;
Mildner, Alexander ;
Cohen, Nadav ;
Jung, Steffen ;
Tanay, Amos ;
Amit, Ido .
SCIENCE, 2014, 343 (6172) :776-779