Quantification of escape from X chromosome inactivation with single-cell omics data reveals heterogeneity across cell types and tissues
Yoshihiko Tomofuji, Ryuya Edahiro, Kyuto Sonehara, Yuya Shirai, Kian Hong Kock, Qingbo S. Wang, Shinichi Namba, Jonathan Moody, Yoshinari Ando, Akari Suzuki, Tomohiro Yata, Kotaro Ogawa, Tatsuhiko Naito, Ho Namkoong, Quy Xiao Xuan Lin, Eliora Violain Buyamin, Le Min Tan, Radhika Sonthalia, Kyung Yeon Han, Hiromu Tanaka, Ho Lee, Varodom Charoensawan, Chung-Chau Hon, Partha P. Majumder, Ponpan Matangkasombut, Woong-Yang Park, Shyam Prabhakar, Jay W. Shin, Piero Carninci, John C. Chambers, Marie Loh, Manop Pithukpakorn, Bhoom Suktitipat, Kazuhiko Yamamoto, Deepa Rajagopalan, Nirmala Arul Rayan, Shvetha Sankaran, Juthamard Chantaraamporn, Ankita Chatterjee, Supratim Ghosh, Kyung Yeon Han, Damita Jevapatarakul, Sarintip Nguantad, Sumanta Sarkar, Narita Thungsatianpun, Mai Abe, Seiko Furukawa, Gyo Inoue, Keiko Myouzen, Jin‐Mi Oh, Akari Suzuki, Yoshinari Ando, Miki Kojima, Tsukasa Kouno, Jinyeong Lim, Arindam Maitra, Le Min Tan, Prasanna Nori Venkatesh, Murim Choi, Jong‐Eun Park, Eliora Violain Buyamin, Kian Hong Kock, Quy Xiao Xuan Lin, Jonathan Moody, Radhika Sonthalia, Kazuyoshi Ishigaki, Masahiro Nakano, Yukinori Okada, Yoshihiko Tomofuji, Ho Namkoong, Ryuya Edahiro, Tomomi Takano, Hiroshi Nishihara, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Shuhei Azekawa, Yohei Mikami, Ho Lee, Takanori Hasegawa, Koji Okudela, Daisuke Okuzaki, Daisuke Motooka, Masahiro Kanai, Tatsuhiko Naito, Kenichi Yamamoto, Qingbo S. Wang, Ryunosuke Saiki, Rino Ishihara, Yuta Matsubara, Junko Hamamoto, Hiroyuki Hayashi, Yukihiro Yoshimura, Natsuo Tachikawa, Emmy Yanagita, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Yasuhiro Kato, Takayoshi Morita
Abstract
Several X-linked genes escape from X chromosome inactivation (XCI), while differences in escape across cell types and tissues are still poorly characterized. Here, we developed scLinaX for directly quantifying relative gene expression from the inactivated X chromosome with droplet-based single-cell RNA sequencing (scRNA-seq) data. The scLinaX and differentially expressed gene analyses with large-scale blood scRNA-seq datasets consistently identified the stronger escape in lymphocytes than in myeloid cells. An extension of scLinaX to a 10x multiome dataset (scLinaX-multi) suggested a stronger escape in lymphocytes than in myeloid cells at the chromatin-accessibility level. The scLinaX analysis of human multiple-organ scRNA-seq datasets also identified the relatively strong degree of escape from XCI in lymphoid tissues and lymphocytes. Finally, effect size comparisons of genome-wide association studies between sexes suggested the underlying impact of escape on the genotype-phenotype association. Overall, scLinaX and the quantified escape catalog identified the heterogeneity of escape across cell types and tissues.