ArticleProceedings of the National Academy of Sciences of the United States of America2018
Extensive cellular heterogeneity of X inactivation revealed by single-cell allele-specific expression in human fibroblasts.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed.
- Escape from X-chromosome inactivation: from gene discovery to regulatory mechanisms.Biochemical Society transactions · 2026Review
- Monoallelic Gene Expression: Stochastic or Clonal? From Detection to Mechanisms and Clinical Significance.International journal of molecular sciences · 2026Review
- Review
- Escape from X inactivation varies across genes and tissues and shapes sex-biased sex chromosome gene expression.BMC genomics · 2026Article
- Dynamic allele usage of X-linked genes ameliorates neurodevelopmental disease phenotypes in brain organoids.Nature communications · 2026Article
- STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling.iScience · 2025Article
- MCT8 Deficiency in Females.The Journal of clinical endocrinology and metabolism · 2025Article
- Exploration of a DDX3X Gene Supplementation Therapy Including Expanded Characterization and Novel Findings of Sleep Disturbances inBiological psychiatry global open science · 2025Article
- XIST Loss Induces Variable Transcriptional Responses Dependent on Cell States.Non-coding RNA · 2025Article
- Leveraging multiomic approaches to elucidate mechanisms of heterogeneity in Alzheimer's disease: Neuropsychiatric symptoms, co-pathologies, and sex differences.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X.Nature communications · 2025Article
- Aging activates escape of the silent X chromosome in the female mouse hippocampus.Science advances · 2025Article
- 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 · 2025Article
- Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals.bioRxiv : the preprint server for biology · 2024Article
- Stable and robust Xi and Y transcriptomes drive cell-type-specific autosomal and Xa responses in vivo and in vitro in four human cell types.Cell genomics · 2024Article
- Quantification of escape from X chromosome inactivation with single-cell omics data reveals heterogeneity across cell types and tissues.Cell genomics · 2024Article
- Evolutionary and biomedical implications of sex differences in the primate brain transcriptome.Cell genomics · 2024Article
- Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting.Nature communications · 2024Article
- Sex-biased gene expression during neural differentiation of human embryonic stem cells.Frontiers in cell and developmental biology · 2024Article
- Lessons from two series by physicians and caregivers' self-reported data in DDX3X-related disorders.Molecular genetics & genomic medicine · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-chromosome inactivation (XCI) provides a dosage compensation mechanism where, in each female cell, one of the two X chromosomes is randomly silenced. However, some genes on the inactive X chromosome and outside the pseudoautosomal regions escape from XCI and are expressed from both alleles (escapees). We investigated XCI at single-cell resolution combining deep single-cell RNA sequencing with whole-genome sequencing to examine allelic-specific expression in 935 primary fibroblast and 48 lymphoblastoid single cells from five female individuals. In this framework we integrated an original method to identify and exclude doublets of cells. In fibroblast cells, we have identified 55 genes as escapees including five undescribed escapee genes. Moreover, we observed that all genes exhibit a variable propensity to escape XCI in each cell and cell type and that each cell displays a distinct expression profile of the escapee genes. A metric, the Inactivation Score-defined as the mean of the allelic expression profiles of the escapees per cell-enables us to discover a heterogeneous and continuous degree of cellular XCI with extremes represented by "inactive" cells, i.e., cells exclusively expressing the escaping genes from the active X chromosome and "escaping" cells expressing the escapees from both alleles. We found that this effect is associated with cell-cycle phases and, independently, with the XIST expression level, which is higher in the quiescent phase (G0). Single-cell allele-specific expression is a powerful tool to identify novel escapees in different tissues and provide evidence of an unexpected cellular heterogeneity of XCI.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.