ArticleNature cell biology2023
DNMT3A-coordinated splicing governs the stem state switch towards differentiation in embryonic and haematopoietic stem cells.
Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 27 citations in OpenAlex.
- The SF3b complex in cancer: structural basis, molecular mechanisms, and therapeutic opportunities.Blood advances · 2026Review
- In vivo CRISPR screens identify dual functions of DNMT3A in mediating tumor immune evasion.Nature communications · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Long-read cDNA sequencing reveals novel isoforms and spliceosome-mutant-enriched transcripts in AML and MDS.bioRxiv : the preprint server for biology · 2026Article
- Mechanical Signaling Regulates DNA Methylation to Maintain Muscle Stem Cell Quiescence.bioRxiv : the preprint server for biology · 2026Article
- Dynamic epigenetic regulation of BCLAF1 splicing in acute myeloid leukemia.Cell death & disease · 2026Article
- DNMT3A R882H Is Not Required for Disease Maintenance in Primary Human AML but Is Associated with Increased Leukemia Stem Cell Frequency.Cancer discovery · 2026Article
- Space-associated stem cell hallmarks of aging and resilience in astronauts.Cell stem cell · 2025Article
- Reconstruction of hematopoietic stem cell nichesMaterials today. Bio · 2025Review
- Single-cell profiling reveals three endothelial-to-hematopoietic transitions with divergent isoform expression landscapes.Nature cardiovascular research · 2025Article
- Transcriptomic Comparisons of Somatic and Cancer Stem Cells.Biomedicines · 2025Review
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Article
- DNMT3A regulates murine megakaryocyte-biased hematopoietic stem cell fate decisions.Blood advances · 2025Article
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- DNA methylation in mammalian development and disease.Nature reviews. Genetics · 2025Review
- Clonal hematopoiesis and hematological malignancy.The Journal of clinical investigation · 2024Review
- Epigenetic modifications in hematopoietic ecosystem: a key tuner from homeostasis to acute myeloid leukemia.Blood science (Baltimore, Md.) · 2024Review
- Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging.Cell stem cell · 2024Article
- Zygotic Splicing Activation of the Transcriptome is a Crucial Aspect of Maternal-to-Zygotic Transition and Required for the Conversion from Totipotency to Pluripotency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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22 authors at 3 institutions in 1 country.
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Abstract
Upon stimulation by extrinsic stimuli, stem cells initiate a programme that enables differentiation or self-renewal. Disruption of the stem state exit has catastrophic consequences for embryogenesis and can lead to cancer. While some elements of this stem state switch are known, major regulatory mechanisms remain unclear. Here we show that this switch involves a global increase in splicing efficiency coordinated by DNA methyltransferase 3α (DNMT3A), an enzyme typically involved in DNA methylation. Proper activation of murine and human embryonic and haematopoietic stem cells depends on messenger RNA processing, influenced by DNMT3A in response to stimuli. DNMT3A coordinates splicing through recruitment of the core spliceosome protein SF3B1 to RNA polymerase and mRNA. Importantly, the DNA methylation function of DNMT3A is not required and loss of DNMT3A leads to impaired splicing during stem cell turnover. Finally, we identify the spliceosome as a potential therapeutic target in DNMT3A-mutated leukaemias. Together, our results reveal a modality through which DNMT3A and the spliceosome govern exit from the stem state towards differentiation.
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