ArticleGenome biology2021
Identification of X-chromosomal genes that drive sex differences in embryonic stem cells through a hierarchical CRISPR screening approach.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 73 citations in OpenAlex.
- A panel of Diversity Outbred mouse embryonic stem cells: enabling the functional characterization of natural genetic variationbioRxiv : the preprint server for biology · 2026Article
- Chromosome X dosage modulates development of aneuploidy in genetically diverse mouse embryonic stem cells.Stem cell reports · 2026Article
- Dynamic allele usage of X-linked genes ameliorates neurodevelopmental disease phenotypes in brain organoids.Nature communications · 2026Article
- Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus.Nature structural & molecular biology · 2025Article
- Xist condensates: perspectives for therapeutic intervention.Genome biology · 2025Review
- Sceptic: pseudotime analysis for time-series single-cell sequencing and imaging data.Genome biology · 2025Article
- Sex and gender differences during the lung lifespan: unveiling a pivotal impact.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- The interferon γ pathway enhances pluripotency and X-chromosome reactivation in iPSC reprogramming.Science advances · 2024Article
- Genome-scale CRISPR-Cas9 screening in stem cells: theories, applications and challenges.Stem cell research & therapy · 2024Review
- X-chromosome inactivation in human iPSCs provides insight into X-regulated gene expression in autosomes.Genome biology · 2024Article
- Establishment and maintenance of random monoallelic expression.Development (Cambridge, England) · 2024Review
- Sex in cardiovascular disease: Why this biological variable should be considered in in vitro models.Science advances · 2024Review
- Epigenetic and Transcriptional Shifts in Human Neural Stem Cells after Reprogramming into Induced Pluripotent Stem Cells and Subsequent Redifferentiation.International journal of molecular sciences · 2024Article
- Roles of the Rlim-Rex1 axis during X chromosome inactivation in mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State.Cell & bioscience · 2023Article
- International society of sports nutrition position stand: nutritional concerns of the female athlete.Journal of the International Society of Sports Nutrition · 2023Review
- Modeling unveils sex differences of signaling networks in mouse embryonic stem cells.Molecular systems biology · 2023Article
- GATA transcription factors drive initial Xist upregulation after fertilization through direct activation of long-range enhancers.Nature cell biology · 2023Article
- CasTuner is a degron and CRISPR/Cas-based toolkit for analog tuning of endogenous gene expression.Nature communications · 2023Article
- The compleX balancing act of controlling X-chromosome dosage and how it impacts mammalian germline development.The Biochemical journal · 2023Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundX-chromosomal genes contribute to sex differences, in particular during early development, when both X chromosomes are active in females. Double X-dosage shifts female pluripotent cells towards the naive stem cell state by increasing pluripotency factor expression, inhibiting the differentiation-promoting MAP kinase (MAPK) signaling pathway, and delaying differentiation.
resultsTo identify the genetic basis of these sex differences, we use a two-step CRISPR screening approach to comprehensively identify X-linked genes that cause the female pluripotency phenotype in murine embryonic stem cells. A primary chromosome-wide CRISPR knockout screen and three secondary screens assaying for different aspects of the female pluripotency phenotype allow us to uncover multiple genes that act in concert and to disentangle their relative roles. Among them, we identify Dusp9 and Klhl13 as two central players. While Dusp9 mainly affects MAPK pathway intermediates, Klhl13 promotes pluripotency factor expression and delays differentiation, with both factors jointly repressing MAPK target gene expression.
conclusionsHere, we elucidate the mechanisms that drive sex-induced differences in pluripotent cells and our approach serves as a blueprint to discover the genetic basis of the phenotypic consequences of other chromosomal effects.
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