ArticleStem cell reports2025
Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation.
Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Disrupted inhibitory interneuron development in SCN1A Dravet syndrome revealed by patient-derived subpallial organoids.Epilepsia · 2026Article
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- Neural peer pressure: intercellular dynamics and emergent phenotypes in the mosaic Rett syndrome brain.Cell communication and signaling : CCS · 2026Review
- Cell-type specific allelic dampening of sex-linked genes in sex chromosome aneuploidy.bioRxiv : the preprint server for biology · 2026Article
- Diversity-in-a-dish: A practical framework for hiPSC model development.Stem cell reports · 2026Review
- Female iPSC X-chromosome inactivation (XCI) erosion and its transcriptomic effects during CRISPR gene editing and neural differentiation.bioRxiv : the preprint server for biology · 2026Article
- Lyonization of X-chromosome: New insights.Journal of genetics · 2026Review
- The impact of X chromosome inactivation on human health.Frontiers in genetics · 2026Review
- Impact of somatic XIST deletions on ongoing XIST expression and inactive X silencing and heterochromatin.Human molecular genetics · 2025Article
- A human induced pluripotent stem cell toolbox for studying sex chromosome effects.Stem cell reports · 2025Article
- X-linked transcriptome dysregulation across immune cells in systemic lupus erythematosus.Biology of sex differences · 2025Article
- Article
- A stem cell-based toolkit to model Angelman syndrome caused by paternal uniparental disomy of chromosome 15.Human cell · 2025Article
- XIST Loss Induces Variable Transcriptional Responses Dependent on Cell States.Non-coding RNA · 2025Article
- Induced Pluripotent (iPSC) and Mesenchymal (MSC) Stem Cells for In Vitro Disease Modeling and Regenerative Medicine.International journal of molecular sciences · 2025Review
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Authors and funding
14 authors.
Funding
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Abstract
Female human induced pluripotent stem cells frequently undergo X-chromosome inactivation (XCI) erosion, marked by X-inactive specific transcript (XIST) RNA loss and partial reactivation of the inactive X (Xi). This overlooked phenomenon limits our understanding of its impact on stem cell applications. Here, we show that XCI erosion is frequent and heterogeneous, leading to the reactivation of several X-linked genes. These are primarily located on the short arm of the X chromosome, particularly near escape genes and within H3K27me3-enriched domains, with reactivation linked to reduced promoter DNA methylation. Interestingly, escape genes further increase their expression from Xi upon XCI erosion, highlighting the critical role of XIST in their dosage regulation. Importantly, global (hydroxy)methylation levels and imprinted regions remain unaffected, and analysis of trilineage commitment and cardiomyocyte formation reveals that XCI erosion persists across differentiation. These findings underscore the need for greater awareness of the implications of XCI erosion for stem cell research and clinical applications.
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