An atlas of transcribed enhancers across helper T cell diversity for decoding human diseases
Akiko Oguchi, Akari Suzuki, S Komatsu, Hiroyuki Yoshitomi, Shruti Bhagat, Raku Son, Raoul J.P. Bonnal, Shohei Kojima, Masaru Koido, Kazuhiro Takeuchi, Keiko Myouzen, Gyo Inoue, Tomoya Hirai, Hiromi Sano, Yujiro Takegami, Ai Kanemaru, Itaru Yamaguchi, Yuki Ishikawa, Nao Tanaka, Shigeki Hirabayashi, Yuki Ishikawa, Sho Sekito, Takahiro Inoue, Juha Kere, Shunichi Takeda, Akifumi Takaori‐Kondo, Itaru Endo, Shinpei Kawaoka, Hideya Kawaji, Kazuyoshi Ishigaki, Hideki Ueno, Yoshihide Hayashizaki, Massimiliano Pagani, Piero Carninci, Motoko Yanagita, Nicholas F. Parrish, Chikashi Terao, Kazuhiko Yamamoto, Yasuhiro Murakawa, Matteo M. Guerrini, Hiroaki Hatano, Kazuyoshi Ishigaki, Yuki Ishikawa, S Komatsu, Michihiro Kono, Yasuhiro Murakawa, M Nakano, Akiko Oguchi, Raku Son, Akari Suzuki, Kazuhiro Takeuchi, Nao Tanaka, Chikashi Terao, Kohei Tomizuka, Kazuhiko Yamamoto, Soichiro Yoshino, Kazuhiro Takeuchi, Nao Tanaka, Chikashi Terao, Kohei Tomizuka, Kazuhiko Yamamoto, Soichiro Yoshino
Abstract
Transcribed enhancer maps can reveal nuclear interactions underpinning each cell type and connect specific cell types to diseases. Using a 5′ single-cell RNA sequencing approach, we defined transcription start sites of enhancer RNAs and other classes of coding and noncoding RNAs in human CD4 + T cells, revealing cellular heterogeneity and differentiation trajectories. Integration of these datasets with single-cell chromatin profiles showed that active enhancers with bidirectional RNA transcription are highly cell type–specific and that disease heritability is strongly enriched in these enhancers. The resulting cell type–resolved multimodal atlas of bidirectionally transcribed enhancers, which we linked with promoters using fine-scale chromatin contact maps, enabled us to systematically interpret genetic variants associated with a range of immune-mediated diseases.