ArticleGenome biology2024
X-chromosome inactivation in human iPSCs provides insight into X-regulated gene expression in autosomes.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed.
- Chromosome X dosage modulates development of aneuploidy in genetically diverse mouse embryonic stem cells.Stem cell reports · 2026Article
- Neural peer pressure: intercellular dynamics and emergent phenotypes in the mosaic Rett syndrome brain.Cell communication and signaling : CCS · 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
- "Time Is Brain" - for Cell Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Escape from X inactivation is directly modulated by Xist noncoding RNA.Nature cell biology · 2026Article
- The impact of X chromosome inactivation on human health.Frontiers in genetics · 2026Review
- Clinical characterization and molecular analysis of X-linked juvenile retinoschisis in a northern Chinese cohort.Frontiers in genetics · 2026Article
- 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
- XIST Loss Induces Variable Transcriptional Responses Dependent on Cell States.Non-coding RNA · 2025Article
- Ancestral genomic functional differences in oligodendroglia: implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation.Stem cell reports · 2025Article
- Epigenetic deprogramming by disruption of CIZ1-RNA nuclear assemblies in early-stage breast cancers.The Journal of cell biology · 2025Article
- Comprehensive multimodal and multiomic profiling reveals epigenetic and transcriptional reprogramming in lung tumors.Communications biology · 2025Article
- Compensation of gene dosage on the mammalian X.Development (Cambridge, England) · 2024Review
- X-chromosome inactivation in human iPSCs provides insight into X-regulated gene expression in autosomes.Genome biology · 2024Article
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4 authors.
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Abstract
backgroundVariation in X chromosome inactivation (XCI) in human-induced pluripotent stem cells (hiPSCs) can impact their ability to model biological sex biases. The gene-wise landscape of X chromosome gene dosage remains unresolved in female hiPSCs. To characterize patterns of de-repression and escape from inactivation, we performed a systematic survey of allele specific expression in 165 female hiPSC lines.
resultsXCI erosion is non-random and primarily affects genes that escape XCI in human tissues. Individual genes and cell lines vary in the frequency and degree of de-repression. Bi-allelic expression increases gradually after modest decrease of XIST in cultures, whose loss is commonly used to mark lines with eroded XCI. We identify three clusters of female lines at different stages of XCI. Increased XCI erosion amplifies female-biased expression at hypomethylated sites and regions normally occupied by repressive histone marks, lowering male-biased differences in the X chromosome. In autosomes, erosion modifies sex differences in a dose-dependent way. Male-biased genes are enriched for hypermethylated regions, and de-repression of XIST-bound autosomal genes in female lines attenuates normal male-biased gene expression in eroded lines. XCI erosion can compensate for a dominant loss of function effect in several disease genes.
conclusionsWe present a comprehensive view of X chromosome gene dosage in hiPSCs and implicate a direct mechanism for XCI erosion in regulating autosomal gene expression in trans. The uncommon and variable reactivation of X chromosome genes in female hiPSCs can provide insight into X chromosome's role in regulating gene expression and sex differences in humans.
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