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 & 6 others Timo Lassmann, Chung Chau Hon, Erik Arner, Piero Carninci, Charles Plessy, Jay W. Shin

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 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-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.

Original languageEnglish
Article number360
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Fingerprint

resolution cell
Transcription Initiation Site
Cells
cells
multiplexing
Multiplexing
Microfluidics
strands
lungs
set theory
bursts
cancer
Fluorescence
RNA
fluorescence
Molecules
profiles
Fluorescence In Situ Hybridization
Transcriptome
molecules

Cite this

Kouno, T., Moody, J., Kwon, A. T. J., Shibayama, Y., Kato, S., Huang, Y., ... Shin, J. W. (2019). C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution. Nature Communications, 10(1), [360]. https://doi.org/10.1038/s41467-018-08126-5
Kouno, Tsukasa ; Moody, Jonathan ; Kwon, Andrew Tae Jun ; Shibayama, Youtaro ; Kato, Sachi ; Huang, Yi ; Böttcher, Michael ; Motakis, Efthymios ; Mendez, Mickaël ; Severin, Jessica ; Luginbühl, Joachim ; Abugessaisa, Imad ; Hasegawa, Akira ; Takizawa, Satoshi ; Arakawa, Takahiro ; Furuno, Masaaki ; Ramalingam, Naveen ; West, Jay ; Suzuki, Harukazu ; Kasukawa, Takeya ; Lassmann, Timo ; Hon, Chung Chau ; Arner, Erik ; Carninci, Piero ; Plessy, Charles ; Shin, Jay W. / C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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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 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-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.",
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Kouno, T, Moody, J, Kwon, ATJ, Shibayama, Y, Kato, S, Huang, Y, Böttcher, M, Motakis, E, Mendez, M, Severin, J, Luginbühl, J, Abugessaisa, I, Hasegawa, A, Takizawa, S, Arakawa, T, Furuno, M, Ramalingam, N, West, J, Suzuki, H, Kasukawa, T, Lassmann, T, Hon, CC, Arner, E, Carninci, P, Plessy, C & Shin, JW 2019, 'C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution' Nature Communications, vol. 10, no. 1, 360. https://doi.org/10.1038/s41467-018-08126-5

C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution. / Kouno, Tsukasa; Moody, Jonathan; Kwon, Andrew Tae Jun; Shibayama, Youtaro; Kato, Sachi; Huang, Yi; Böttcher, Michael; Motakis, Efthymios; Mendez, Mickaël; Severin, Jessica; Luginbühl, Joachim; Abugessaisa, Imad; Hasegawa, Akira; Takizawa, Satoshi; Arakawa, Takahiro; Furuno, Masaaki; Ramalingam, Naveen; West, Jay; Suzuki, Harukazu; Kasukawa, Takeya; Lassmann, Timo; Hon, Chung Chau; Arner, Erik; Carninci, Piero; Plessy, Charles; Shin, Jay W.

In: Nature Communications, Vol. 10, No. 1, 360, 01.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution

AU - Kouno, Tsukasa

AU - Moody, Jonathan

AU - Kwon, Andrew Tae Jun

AU - Shibayama, Youtaro

AU - Kato, Sachi

AU - Huang, Yi

AU - Böttcher, Michael

AU - Motakis, Efthymios

AU - Mendez, Mickaël

AU - Severin, Jessica

AU - Luginbühl, Joachim

AU - Abugessaisa, Imad

AU - Hasegawa, Akira

AU - Takizawa, Satoshi

AU - Arakawa, Takahiro

AU - Furuno, Masaaki

AU - Ramalingam, Naveen

AU - West, Jay

AU - Suzuki, Harukazu

AU - Kasukawa, Takeya

AU - Lassmann, Timo

AU - Hon, Chung Chau

AU - Arner, Erik

AU - Carninci, Piero

AU - Plessy, Charles

AU - Shin, Jay W.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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-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.

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U2 - 10.1038/s41467-018-08126-5

DO - 10.1038/s41467-018-08126-5

M3 - Article

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JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

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