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December 8, 2025BloodOpen Access

TET2 mutations drive cell-autonomous type I interferon production and selective advantage through TRIM4 silencing

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Authors

MJManon JaudLTLewis E. TomalinCFChih-Wei Fan

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Overview

Experimental models show TET2 mutations drive type I interferon production in hematopoietic stem and progenitor cells, highlighting TRIM4 silencing's role in clonal hematopoiesis.

Key Points

  • This research aims to elucidate the mechanisms by which TET2 mutations affect hematopoietic stem and progenitor cells and lead to clonal hematopoiesis.
  • Developed human isogenic induced pluripotent stem cell models
  • Performed integrated transcriptome and DNA methylation analyses
  • Conducted single-cell RNA-seq and immunoblotting experiments
  • Used CRISPR/Cas9 for knockout experiments
  • Evaluated competitive repopulation assays in NSGS mice.
  • TET2 mutations induced cell-autonomous type I interferon production
  • TRIM4 silencing was identified as a key effector of TET2 deficiency
  • Mutant HSPCs demonstrated a selective growth advantage over wild-type cells
  • Blocking type I interferon signaling reduced the expansion of TET2-deficient cells
  • Identified DHX58 as a positive regulator mediating aberrant interferon production.

Cite This Study

Jaud et al. (2025) studied this question.

synapsesocial.com/papers/69362f764fa91c937236e36dhttps://doi.org/10.1182/blood-2025-976
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Also Consider

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

  1. 1TET2 Deficiency Increases the Competitive Advantage of Hematopoietic Stem Cells through Upregulation of Thrombopoietin Receptor Signaling2024
  2. 2Perturbation of iNKT differentiation during clonal hematopoiesis from rewiring of inflammation and lipid presentation2025
  3. 3Loss of TET function in T regulatory cells yields Tfh-like ex-Treg cells with the features of heterochromatin dysfunction 22665332026
  4. 4Chromodomain helicase DNA binding protein CHD2 interacts with TET2 and regulates lineage defining transcription in hematopoietic stem and progenitor cells2025
  5. 5Single-cell multiomic profiling of gene mutation, chromatin accessibility, and gene expression in TET2-mutant clonal hematopoiesis2025