ArticleThe EMBO journal2021
Cooperative genetic networks drive embryonic stem cell transition from naïve to formative pluripotency.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- Integration of the naive pluripotency gene network with the response to GSK3 inhibition by Tcf7l1-driven enhancer decommissioning.Stem cell reports · 2026Article
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- Unveiling gene perturbation effects through gene regulatory networks inference from single-cell transcriptomic data.PLoS computational biology · 2026Article
- Exit from naive pluripotency proceeds with variable latency but without asymmetric division to generate population heterogeneity.Stem cell reports · 2026Article
- Ribosome biogenesis as a potential therapeutic target in KRAS mutant colorectal cancer.Nature communications · 2025Article
- Acetylation of lysine 49 on Ctnnb1 drives naïve pluripotency in murine stem cells by modulating Nanog function.PNAS nexus · 2025Article
- The exit from naive pluripotency: a platform for the study of enhancer mechanistics.Biochemical Society transactions · 2025Review
- Novel kinetic and developmental transcriptomic pan-stress responses by embryonic stem cells.Scientific reports · 2025Article
- Med12 cooperates with multiple differentiation signals to facilitate efficient lineage transitions in embryonic stem cells.Journal of cell science · 2025Article
- The regulatory architecture of the primed pluripotent cell state.Nature communications · 2025Article
- Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness.Nature communications · 2024Article
- FoxO transcription factors actuate the formative pluripotency specific gene expression programme.Nature communications · 2024Article
- Gene regulatory networks in disease and ageing.Nature reviews. Nephrology · 2024Review
- Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.Genome biology · 2024Article
- Enhancer-promoter interactions are reconfigured through the formation of long-range multiway hubs as mouse ES cells exit pluripotency.Molecular cell · 2024Article
- SRRM2 splicing factor modulates cell fate in early development.Biology open · 2024Article
- Pluripotency state transition of embryonic stem cells requires the turnover of histone chaperone FACT on chromatin.iScience · 2024Article
- The Nucleosome Remodelling and Deacetylation complex coordinates the transcriptional response to lineage commitment in pluripotent cells.Biology open · 2024Article
- Haploid-genetic screening of trophectoderm specification identifiesScience advances · 2023Article
- The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation.Nature communications · 2023Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
In the mammalian embryo, epiblast cells must exit the naïve state and acquire formative pluripotency. This cell state transition is recapitulated by mouse embryonic stem cells (ESCs), which undergo pluripotency progression in defined conditions in vitro. However, our understanding of the molecular cascades and gene networks involved in the exit from naïve pluripotency remains fragmentary. Here, we employed a combination of genetic screens in haploid ESCs, CRISPR/Cas9 gene disruption, large-scale transcriptomics and computational systems biology to delineate the regulatory circuits governing naïve state exit. Transcriptome profiles for 73 ESC lines deficient for regulators of the exit from naïve pluripotency predominantly manifest delays on the trajectory from naïve to formative epiblast. We find that gene networks operative in ESCs are also active during transition from pre- to post-implantation epiblast in utero. We identified 496 naïve state-associated genes tightly connected to the in vivo epiblast state transition and largely conserved in primate embryos. Integrated analysis of mutant transcriptomes revealed funnelling of multiple gene activities into discrete regulatory modules. Finally, we delineate how intersections with signalling pathways direct this pivotal mammalian cell state transition.
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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.