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December 8, 2025BloodOpen Access

U2AF1S34F mutant HSPCs have a fitness advantage in aged and inflamed bone marrow

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Authors

MDMarco De Dominici

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Overview

Transplantation study shows aging and inflammation enhance expansion of U2AF1S34F mutant HSPCs in bone marrow, indicating implications for myeloid malignancies.

Key Points

  • This research investigates how aging and inflammation affect the selection of U2AF1S34F mutant hematopoietic stem and progenitor cells (HSPCs).
  • Utilized an inducible mouse model with U2AF1S34F mutation.
  • Transplanted cells from aged and young mice into recipient mice of varying ages.
  • Evaluated the expansion of mutant cells in bone marrow and peripheral blood.
  • Conducted single-cell RNA sequencing for gene expression analysis.
  • Young U2AF1S34F mutant cells were selected against in young recipients but expanded in aged recipients.
  • IL-1β treatment reversed negative selection in vitro and promoted expansion in vivo.
  • Gene expression analysis showed downregulation of inflammatory signaling in old mutant HSCs.

Cite This Study

Marco De Dominici (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dd51https://doi.org/10.1182/blood-2025-1395
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Transcriptional and splicing dysregulation by U2AF1 mutations contribute to inflammatory and migratory alterations in MDS2025
  2. 2Bone marrow environmental alterations underlie proliferative clonal expansion in clonal hematopoiesis2025
  3. 3Replicative stress-induced aging of hematopoietic stem progenitor cells increases oncogenic mutation burden and incidence of myelodysplasia in sickle cell disease mice2025
  4. 4Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging2024 · 123 citations
  5. 5Sf3b1+/K700E hematopoietic stem cells create their own expansion niche2025