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, Tatsusada Okuno, Boxiang Liu, Koichi Matsuda, Koichi Fukunaga, Hideki Mochizuki, Woong-Yang Park, Kazuhiko Yamamoto, Chung-Chau Hon, Jay W Shin, Shyam Prabhakar, Atsushi Kumanogoh, Yukinori Okada
{"title":"Quantification of escape from X chromosome inactivation with single-cell omics data reveals heterogeneity across cell types and tissues.","authors":"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, Tatsusada Okuno, Boxiang Liu, Koichi Matsuda, Koichi Fukunaga, Hideki Mochizuki, Woong-Yang Park, Kazuhiko Yamamoto, Chung-Chau Hon, Jay W Shin, Shyam Prabhakar, Atsushi Kumanogoh, Yukinori Okada","doi":"10.1016/j.xgen.2024.100625","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406184/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell genomics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xgen.2024.100625","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.