C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution

被引:65
作者
Kouno, Tsukasa [1 ]
Moody, Jonathan [1 ]
Kwon, Andrew Tae-Jun [1 ]
Shibayama, Youtaro [1 ]
Kato, Sachi [1 ]
Huang, Yi [1 ,3 ]
Bottcher, Michael [1 ]
Motakis, Efthymios [1 ,4 ]
Mendez, Mickael [1 ,5 ]
Severin, Jessica [1 ]
Luginbuhl, Joachim [1 ]
Abugessaisa, Imad [1 ]
Hasegawa, Akira [1 ]
Takizawa, Satoshi [1 ]
Arakawa, Takahiro [1 ]
Furuno, Masaaki [1 ]
Ramalingam, Naveen [2 ]
West, Jay [2 ]
Suzuki, Harukazu [1 ]
Kasukawa, Takeya [1 ]
Lassmann, Timo [1 ,6 ]
Hon, Chung-Chau [1 ]
Arner, Erik [1 ]
Carninci, Piero [1 ]
Plessy, Charles [1 ,7 ]
Shin, Jay W. [1 ]
机构
[1] RIKEN Ctr Integrat Med Sci IMS, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan
[2] Fluidigm Corp, Single Cell Res & Dev, 7000 Shoreline Court,Suite 100, San Francisco, CA 94080 USA
[3] ACT Genom Co Ltd, 3F,345 Xinhu 2nd Rd, Taipei City 114, Taiwan
[4] Natl Univ Singapore, Yong Loo Lin Sch Med MD6, 08-01,14 Med Dr, Singapore 117599, Singapore
[5] Princess Margaret Canc Res, Tower 11-401,101 Coll St, Toronto, ON M5G 1L7, Canada
[6] Univ Western Australia, Perth Childrens Hosp, Telethon Kids Inst, 15 Hosp Ave, Nedlands, WA 6009, Australia
[7] Okinawa Inst Sci & Technol Grad Univ OIST, 1919-1 Tancha, Onna, Okinawa 9040495, Japan
关键词
TGF-BETA; GENE-EXPRESSION; INTEGRATIVE ANALYSIS; VISUALIZATION; ATLAS; DATABASE; DYNAMICS; NANOCAGE; TFAP2C; FUTURE;
D O I
10.1038/s41467-018-08126-5
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
Single-cell transcriptomic profiling is a powerful tool to explore cellular heterogeneity. However, most of these methods focus on the 3'-end of polyadenylated transcripts and provide only a partial view of the transcriptome. We introduce C1 CAGE, a method for the detection of transcript 5'-ends with an original sample multiplexing strategy in the C1 (TM) microfluidic system. We first quantifiy the performance of C1 CAGE and find it as accurate and sensitive as other methods in the C1 system. We then use it to profile promoter and enhancer activities in the cellular response to TGF-beta of lung cancer cells and discover subpopulations of cells differing in their response. We also describe enhancer RNA dynamics revealing transcriptional bursts in subsets of cells with transcripts arising from either strand in a mutually exclusive manner, validated using single molecule fluorescence in situ hybridization.
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页数:12
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