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DNMT3A regulates megakaryocyte-biased hematopoietic stem cell fate decisions [RNA-Seq]

GSE287995 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/02/17 Platform GPL24247
Summary
Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of the peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but no differential regulatory mechanisms have been identified. Here, we considered whether DNA methyltransferase 3A (DNMT3A) has a role in determining the differentiation choice of HSCs. We find that the most primitive megakaryocyte-biased HSCs depend most on DNMT3A for efficient hematopoietic regeneration, particularly of the lymphoid lineages. Reduced DNMT3A amplifies the biased HSC behavior. DNMT3A also regulates megakaryocyte and platelet output in part through DNA methylation at key megakaryocyte lineage loci. Together, our findings establish the role of epigenetic regulation in the fate of megakaryocyte-biased HSCs and their downstream progeny and suggest that the outcomes of DNMT3A-mutant clonal hematopoiesis and malignancies might vary depending on the identity of the HSC that acquires the mutation.
Published in
DNMT3A regulates murine megakaryocyte-biased hematopoietic stem cell fate decisions
Waldvogel SM, Camacho V, Fan D et al. · Blood advances 2025 · PMID 40048738 · doi:10.1182/bloodadvances.2024015061
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Also filed as BioProject PRJNA1215424 and SRA study SRP559774. Searching any of these in the dataset finder brings you back here.

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