A single-cell atlas of transcribed cis-regulatory elements in the human genome

Transcribed cis-regulatory elements (tCREs), such as promoters and enhancers, are fundamental to modulate gene expression and define cell identity. The detailed mapping of tCREs at single-cell resolution is essential for understanding the regulatory mechanisms that govern cellular functions. Prior t...

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Main Authors Moody, Jonathan, Kouno, Tsukasa, Kojima, Miki, Koya, Ikuko, Leon, Julio, Suzuki, Akari, Hasegawa, Akira, Akiyama, Taishin, Akiyama, Nobuko, Amagai, Masayuki, Jen-Chien, Chang, Fukushima-Nomura, Ayano, Handa, Mika, Hino, Kazunori, Hino, Mizuki, Hirata, Tomoko, Imai, Yuuki, Inoue, Kazunori, Kawasaki, Hiroshi, Kimura, Toshihiro, Kinoshita, Tomofumi, Kubo, Ken-Ichiro, Kunii, Yasuto, Lopez-Redondo, Fernando, Manabe, Ri-Ichiroh, Miyai, Tomohiro, Morimoto, Satoru, Nagaoka, Atsuko, Nakajima, Jun, Noma, Shohei, Okazaki, Yasushi, Ozaki, Kokoro, Saeki, Noritaka, Sakai, Hiroshi, Seyama, Kuniaki, Shibayama, Youtaro, Sujino, Tomohisa, Tagami, Michihira, Takahashi, Hayato, Masaki Takao, Takeshita, Masaru, Takiuchi, Tsuyoshi, Terao, Chikashi, Yip, Chi Wai, Yoshinaga, Satoshi, Okano, Hideyuki, Yamamoto, Kazuhiko, Takeya Kasukawa, Ando, Yoshinari, Carninci, Piero, Shin, Jay W, Chung-Chau, Hon
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Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 14.11.2023
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Abstract Transcribed cis-regulatory elements (tCREs), such as promoters and enhancers, are fundamental to modulate gene expression and define cell identity. The detailed mapping of tCREs at single-cell resolution is essential for understanding the regulatory mechanisms that govern cellular functions. Prior tCRE catalogs, limited by bulk analysis, have often overlooked cellular heterogeneity. We have constructed a tCRE atlas using single-cell 5-RNA-seq, capturing over 340,000 single-cells from 23 human tissues and annotating more than 175,000 tCREs, substantially enhancing the scope and granularity of existing cis-regulatory element annotations in the human genome. This atlas unveils patterns of gene regulation, revealing connections between broadly expressed promoters and cell type-specific distal tCREs. Assessing trait heritability at single-cell resolution with a novel tCRE module-based approach, we uncovered the nuanced trait-gene regulatory relationships across a continuum of cell populations, offering insights beyond traditional gene-level and bulk-sample analyses. Our study bridges the gap between gene regulation and trait heritability, underscoring the potential of single-cell analysis to elucidate the genetic foundations of complex traits. These insights set the stage for future research to investigate the impact of genetic variations on diseases at the individual level, advancing the understanding of cellular and molecular basis of trait heritability.Competing Interest StatementThe authors have declared no competing interest.Footnotes* https://doi.org/10.6084/m9.figshare.c.6926944
AbstractList Transcribed cis-regulatory elements (tCREs), such as promoters and enhancers, are fundamental to modulate gene expression and define cell identity. The detailed mapping of tCREs at single-cell resolution is essential for understanding the regulatory mechanisms that govern cellular functions. Prior tCRE catalogs, limited by bulk analysis, have often overlooked cellular heterogeneity. We have constructed a tCRE atlas using single-cell 5-RNA-seq, capturing over 340,000 single-cells from 23 human tissues and annotating more than 175,000 tCREs, substantially enhancing the scope and granularity of existing cis-regulatory element annotations in the human genome. This atlas unveils patterns of gene regulation, revealing connections between broadly expressed promoters and cell type-specific distal tCREs. Assessing trait heritability at single-cell resolution with a novel tCRE module-based approach, we uncovered the nuanced trait-gene regulatory relationships across a continuum of cell populations, offering insights beyond traditional gene-level and bulk-sample analyses. Our study bridges the gap between gene regulation and trait heritability, underscoring the potential of single-cell analysis to elucidate the genetic foundations of complex traits. These insights set the stage for future research to investigate the impact of genetic variations on diseases at the individual level, advancing the understanding of cellular and molecular basis of trait heritability.Competing Interest StatementThe authors have declared no competing interest.Footnotes* https://doi.org/10.6084/m9.figshare.c.6926944
Author Seyama, Kuniaki
Handa, Mika
Carninci, Piero
Terao, Chikashi
Yamamoto, Kazuhiko
Fukushima-Nomura, Ayano
Nakajima, Jun
Yoshinaga, Satoshi
Sujino, Tomohisa
Shin, Jay W
Morimoto, Satoru
Masaki Takao
Akiyama, Nobuko
Takiuchi, Tsuyoshi
Hirata, Tomoko
Kojima, Miki
Hino, Kazunori
Okazaki, Yasushi
Kimura, Toshihiro
Hasegawa, Akira
Kawasaki, Hiroshi
Nagaoka, Atsuko
Akiyama, Taishin
Sakai, Hiroshi
Chung-Chau, Hon
Suzuki, Akari
Takeshita, Masaru
Takahashi, Hayato
Yip, Chi Wai
Shibayama, Youtaro
Kunii, Yasuto
Amagai, Masayuki
Noma, Shohei
Leon, Julio
Ando, Yoshinari
Kouno, Tsukasa
Okano, Hideyuki
Tagami, Michihira
Kinoshita, Tomofumi
Ozaki, Kokoro
Miyai, Tomohiro
Saeki, Noritaka
Jen-Chien, Chang
Lopez-Redondo, Fernando
Manabe, Ri-Ichiroh
Koya, Ikuko
Kubo, Ken-Ichiro
Hino, Mizuki
Imai, Yuuki
Takeya Kasukawa
Inoue, Kazunori
Moody, Jonathan
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Snippet Transcribed cis-regulatory elements (tCREs), such as promoters and enhancers, are fundamental to modulate gene expression and define cell identity. The...
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SubjectTerms Enhancers
Gene mapping
Gene regulation
Genetic diversity
Genomes
Heritability
Promoters
Regulatory sequences
Title A single-cell atlas of transcribed cis-regulatory elements in the human genome
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