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

Tsukasa Kouno, Jonathan Moody, Andrew Tae-Jun Kwon, Youtaro Shibayama, Sachi Kato, Yi Huang, Michael Böttcher, Efthymios Motakis, Mickaël Mendez, Jessica Severin, Joachim Luginbühl, Imad Abugessaisa, Akira Hasegawa, Satoshi Takizawa, Takahiro Arakawa, Masaaki Furuno, Naveen Ramalingam, Jay West, Harukazu Suzuki, Takeya Kasukawa, Timo Lassmann, Chung-Chau Hon, Erik Arner, Piero Carninci, Charles Plessy () and Jay W. Shin ()
Additional contact information
Tsukasa Kouno: RIKEN Center for Integrative Medical Sciences (IMS)
Jonathan Moody: RIKEN Center for Integrative Medical Sciences (IMS)
Andrew Tae-Jun Kwon: RIKEN Center for Integrative Medical Sciences (IMS)
Youtaro Shibayama: RIKEN Center for Integrative Medical Sciences (IMS)
Sachi Kato: RIKEN Center for Integrative Medical Sciences (IMS)
Yi Huang: RIKEN Center for Integrative Medical Sciences (IMS)
Michael Böttcher: RIKEN Center for Integrative Medical Sciences (IMS)
Efthymios Motakis: RIKEN Center for Integrative Medical Sciences (IMS)
Mickaël Mendez: RIKEN Center for Integrative Medical Sciences (IMS)
Jessica Severin: RIKEN Center for Integrative Medical Sciences (IMS)
Joachim Luginbühl: RIKEN Center for Integrative Medical Sciences (IMS)
Imad Abugessaisa: RIKEN Center for Integrative Medical Sciences (IMS)
Akira Hasegawa: RIKEN Center for Integrative Medical Sciences (IMS)
Satoshi Takizawa: RIKEN Center for Integrative Medical Sciences (IMS)
Takahiro Arakawa: RIKEN Center for Integrative Medical Sciences (IMS)
Masaaki Furuno: RIKEN Center for Integrative Medical Sciences (IMS)
Naveen Ramalingam: Fluidigm Corporation
Jay West: Fluidigm Corporation
Harukazu Suzuki: RIKEN Center for Integrative Medical Sciences (IMS)
Takeya Kasukawa: RIKEN Center for Integrative Medical Sciences (IMS)
Timo Lassmann: RIKEN Center for Integrative Medical Sciences (IMS)
Chung-Chau Hon: RIKEN Center for Integrative Medical Sciences (IMS)
Erik Arner: RIKEN Center for Integrative Medical Sciences (IMS)
Piero Carninci: RIKEN Center for Integrative Medical Sciences (IMS)
Charles Plessy: RIKEN Center for Integrative Medical Sciences (IMS)
Jay W. Shin: RIKEN Center for Integrative Medical Sciences (IMS)

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract 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 C1TM 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-β 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.

Date: 2019
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DOI: 10.1038/s41467-018-08126-5

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