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A landscape of X-inactivation during human T cell development

Björn Gylemo, Maike Bensberg, Viktoria Hennings, Christina Lundqvist, Alessandro Camponeschi, Dóra Goldmann, Huan Zhang, Aida Selimović-Pašić, Antonio Lentini, Olov Ekwall and Colm E. Nestor ()
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Björn Gylemo: Linköping University
Maike Bensberg: Linköping University
Viktoria Hennings: University of Gothenburg
Christina Lundqvist: University of Gothenburg
Alessandro Camponeschi: University of Gothenburg
Dóra Goldmann: Linköping University
Huan Zhang: Linköping University
Aida Selimović-Pašić: Linköping University
Antonio Lentini: Linköping University
Olov Ekwall: University of Gothenburg
Colm E. Nestor: Linköping University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Females exhibit a more robust immune response to both self-antigens and non-self-antigens than males, resulting in a higher prevalence of autoimmune diseases but more effective responses against infection. Increased expression of X-linked immune genes in female T cells is thought to underlie this enhanced response. Here we isolate thymocytes from pediatric thymi of healthy males (46, XY), females (46, XX), a female with completely skewed X-chromosome inactivation (46, XX, cXCI) and a female with Turner syndrome (45, X0). Using whole exome sequencing, RNA sequencing and DNA methylation data, we present a sex-aware expression profile of T cell development and generate a high-resolution map of escape from X-chromosome inactivation (XCI). Unexpectedly, XCI is transcriptionally and epigenetically stable throughout T cell development, and is independent of expression of XIST, the lncRNA responsible for XCI initiation during early embryonic development. In thymocytes, several genes known to escape XCI are expressed from only one X-chromosome. Additionally, we further reveal that a second X-chromosome is dispensable for T cell development. Our study thus provides a high-resolution map of XCI during human development and suggests a re-evaluation of XCI in sex differences in T cell function.

Date: 2024
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DOI: 10.1038/s41467-024-54110-7

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