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Cell Genomics
Article . 2024 . Peer-reviewed
License: CC BY NC ND
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Cell Genomics
Article . 2024
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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; +193 Authors

Quantification of escape from X chromosome inactivation with single-cell omics data reveals heterogeneity across cell types and tissues

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.

Keywords

Male, Sequence Analysis, RNA, Article, Mice, X Chromosome Inactivation, Organ Specificity, Genes, X-Linked, Humans, Animals, Female, Myeloid Cells, Lymphocytes, Single-Cell Analysis, Genome-Wide Association Study

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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
8
Top 10%
Average
Top 10%
Green
gold