Assessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave’s disease and control
Abstract Background The reactivation and loss of mosaicism hypothesis due to X chromosome inactivation (XCI) skewing and escape could influence gender differences in autoimmune diseases. XCI selectively inactivates one of the two X chromosomes in females. Methods To estimate XCI skewing and the occu...
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2025-01-01
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| Series: | BMC Molecular and Cell Biology |
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| Online Access: | https://doi.org/10.1186/s12860-025-00533-z |
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| author | In-Cheol Baek Soo Yeun Sim Byung-Kyu Suh Tai-Gyu Kim Won Kyoung Cho |
| author_facet | In-Cheol Baek Soo Yeun Sim Byung-Kyu Suh Tai-Gyu Kim Won Kyoung Cho |
| author_sort | In-Cheol Baek |
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| description | Abstract Background The reactivation and loss of mosaicism hypothesis due to X chromosome inactivation (XCI) skewing and escape could influence gender differences in autoimmune diseases. XCI selectively inactivates one of the two X chromosomes in females. Methods To estimate XCI skewing and the occurrence of XCI escape, we conducted a normal female (NF) without a history of autoimmune thyroid disease (AITD) and a patient with Grave’s disease (GD) based on a thyroid diagnosis. After single-cell RNA sequencing, heterozygous variants were converted and transformed. XCI skewing was calculated using the formula and the skewing degree was defined. NF/GD genes were compared using correction methods. Positions are heterozygous within a single cell as indicated by a unique barcode. Results XCI skewing showed 45.8%/48.9% relatively random, 29.4%/27.0% skewing, 24.6%/23.7% severe skewing, and 0.2%/0.4% extreme severe skewing. 24.8%/24.1% in NF/GD exhibited severe skewing or higher. A total of 13 genes were significantly associated with XCI skewing ratios in NF/GD cells. In total, 371/250 nucleotide positions with only one barcode (representing a unique cell) were identified for XCI escape. A total of 143/52 nucleotide positions spanned 20/6 genes, and 12/1 genes were identified as XCI escapes. Conclusions These results could aid in understanding the immunogenetics of gender differences in various autoimmune disease pathophysiologies. |
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| institution | Kabale University |
| issn | 2661-8850 |
| language | English |
| publishDate | 2025-01-01 |
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| series | BMC Molecular and Cell Biology |
| spelling | doaj-art-f6f893a895724785b242ad22fa8ebd792025-02-02T12:47:19ZengBMCBMC Molecular and Cell Biology2661-88502025-01-0126111110.1186/s12860-025-00533-zAssessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave’s disease and controlIn-Cheol Baek0Soo Yeun Sim1Byung-Kyu Suh2Tai-Gyu Kim3Won Kyoung Cho4Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of KoreaDepartment of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDepartment of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDepartment of Microbiology, College of Medicine, The Catholic University of KoreaDepartment of Pediatrics, College of Medicine, St. Vincent’s Hospital, The Catholic University of KoreaAbstract Background The reactivation and loss of mosaicism hypothesis due to X chromosome inactivation (XCI) skewing and escape could influence gender differences in autoimmune diseases. XCI selectively inactivates one of the two X chromosomes in females. Methods To estimate XCI skewing and the occurrence of XCI escape, we conducted a normal female (NF) without a history of autoimmune thyroid disease (AITD) and a patient with Grave’s disease (GD) based on a thyroid diagnosis. After single-cell RNA sequencing, heterozygous variants were converted and transformed. XCI skewing was calculated using the formula and the skewing degree was defined. NF/GD genes were compared using correction methods. Positions are heterozygous within a single cell as indicated by a unique barcode. Results XCI skewing showed 45.8%/48.9% relatively random, 29.4%/27.0% skewing, 24.6%/23.7% severe skewing, and 0.2%/0.4% extreme severe skewing. 24.8%/24.1% in NF/GD exhibited severe skewing or higher. A total of 13 genes were significantly associated with XCI skewing ratios in NF/GD cells. In total, 371/250 nucleotide positions with only one barcode (representing a unique cell) were identified for XCI escape. A total of 143/52 nucleotide positions spanned 20/6 genes, and 12/1 genes were identified as XCI escapes. Conclusions These results could aid in understanding the immunogenetics of gender differences in various autoimmune disease pathophysiologies.https://doi.org/10.1186/s12860-025-00533-zX chromosome inactivationAutoimmune thyroid diseaseSingle nucleotide polymorphismSingle-cell RNA sequencingXCI skewing and escape |
| spellingShingle | In-Cheol Baek Soo Yeun Sim Byung-Kyu Suh Tai-Gyu Kim Won Kyoung Cho Assessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave’s disease and control BMC Molecular and Cell Biology X chromosome inactivation Autoimmune thyroid disease Single nucleotide polymorphism Single-cell RNA sequencing XCI skewing and escape |
| title | Assessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave’s disease and control |
| title_full | Assessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave’s disease and control |
| title_fullStr | Assessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave’s disease and control |
| title_full_unstemmed | Assessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave’s disease and control |
| title_short | Assessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave’s disease and control |
| title_sort | assessment of xci skewing and demonstration of xci escape region based on single cell rna sequencing comparison between female grave s disease and control |
| topic | X chromosome inactivation Autoimmune thyroid disease Single nucleotide polymorphism Single-cell RNA sequencing XCI skewing and escape |
| url | https://doi.org/10.1186/s12860-025-00533-z |
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