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

Tsukasa Kouno, Jonathan Moody, Andrew 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

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Received: 11th June 18

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 quantified the performance of C1 CAGE and found it as accurate and sensitive as other methods in C1 system. We then used it to profile promoter and enhancer activities in the cellular response to TGF-β of lung cancer cells and discovered 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 within a single-cell in a mutually exclusive manner, which was validated using single molecule fluorescence in-situ hybridization.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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