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Nat Commun. 2019 Jan 21;10(1):360. doi: 10.1038/s41467-018-08126-5.

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

Author information

1
RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
2
ACT Genomics Co. Ltd., 3F., No. 345, Xinhu 2nd Rd, Neihu Dist., Taipei City, 114, Taiwan.
3
Yong Loo Lin School of Medicine MD6, #08-01, 14 Medical Drive, National University of Singapore, Singapore, 117599, Singapore.
4
Princess Margaret Cancer Research Tower 11-401, 101 College Street, Toronto, ON, M5G 1L7, Canada.
5
Single-Cell Research and Development, Fluidigm Corporation, 7000 Shoreline Court, Suite 100, South San Francisco, 94080, CA, USA.
6
Telethon Kids Institute, The University of Western Australia, Perth Children's Hospital, 15 Hospital Ave, Nedlands, 6009, WA, Australia.
7
RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. charles.plessy@oist.jp.
8
Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa, 904-0495, Japan. charles.plessy@oist.jp.
9
RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. jay.shin@riken.jp.

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.

PMID:
30664627
PMCID:
PMC6341120
DOI:
10.1038/s41467-018-08126-5
[Indexed for MEDLINE]
Free PMC Article

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