Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
December 8, 2025Blood

Mis-splicing of Mdm4 activates TRP53 and impairs HSPC growth in a mouse model of myelodysplastic syndromes

View Full Paper
Ask AI
Bookmark
Share

Authors

JSJin ShaoJFJennifer A. Foltz

Discussion

Loading...

Member takes

Overview

RNAseq analysis shows splicing factor gene mutations impair growth of HSPCs via TRP53 activation in myelodysplastic syndromes, indicating a critical role of Mdm4 mis-splicing.

Key Points

  • This research aims to investigate how splicing factor gene mutations affect the growth of hematopoietic stem and progenitor cells (HSPCs) through TRP53 activation.
  • Used mouse models with U2af1S34F mutations to study HSPC growth.
  • Employed RNAseq and single-cell RNAseq to analyze gene expression patterns.
  • Conducted competitive bone marrow transplants and co-culture assays to observe the effects of TRP53 activation on HSPCs.
  • Found that TRP53 activation contributes to impaired growth in mutant HSPCs.
  • Demonstrated that deletion of Trp53 partially rescues HSPC growth in vivo.
  • Discovered that overexpression of full-length MDM4 can improve HSPC growth in certain assays.

Cite This Study

Shao et al. (2025) studied this question.

synapsesocial.com/papers/69362f5d4fa91c937236dc6bhttps://doi.org/10.1182/blood-2025-230
View Full Paper
Ask AI
Bookmark
Share

Also Consider

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

  1. 1Examining the role of U2AF1 and TET2 mutations in a myeloid malignancy mouse model2025
  2. 2Transcriptional and splicing dysregulation by U2AF1 mutations contribute to inflammatory and migratory alterations in MDS2025
  3. 3Mutant TP53 allelic states in human hematopoietic stem and progenitor cells2026
  4. 4An actionable DNA repair defect in myeloid malignancies with U2AF1 S34 mutations2025
  5. 5Abstract P03: Splicing factor mutations induce stress granule upregulation in myeloid malignancies2024