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July 22, 2025

Differential sensitivity to LINE 1-induced damage contributes to the expansion of Tet2-deficient HSCs upon chronic inflammatory stress

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Authors

ASAnne STOLZCXChenyuan XuanCFChristelle Freitas

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Overview

Research demonstrates LPS-induced DNA damage in HSCs, highlighting Tet2's role in clonal expansion during inflammation.

Key Points

  • Tet2 deficiency increases the competitiveness of HSCs during chronic inflammation, leading to expanded clonal populations.
  • Chronic inflammation reduces the H3K9me3 mark in wild type HSCs, triggering harmful epigenetic alterations.
  • LINE-1 contributes to DNA damage in WT HSCs under inflammation, negatively affecting clonogenic potential.
  • These findings reveal the importance of epigenetic mechanisms in HSC function and Tet2-mutant cell proliferation.

Cite This Study

STOLZ et al. (2025) studied this question.

synapsesocial.com/papers/689a0614e6551bb0af8cd648https://doi.org/10.1101/2025.07.21.665900
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Also Consider

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

  1. 1Human TET2-mutant clonal hematopoiesis expansion is driven by distinct inflammatory signaling responses in stem cells versus myeloid progeny.2025 · 8 citations
  2. 2Perturbation of iNKT differentiation during clonal hematopoiesis from rewiring of inflammation and lipid presentation2025
  3. 3<i>Id1</i> promotes clonal hematopoiesis in mice with <i>Tet2</i> loss of function2025
  4. 4The bromodomain and extra-terminal domain protein BRD4 promotes both self renewal and inflammation in TET2 mutated clonal hematopoiesis2025
  5. 5Bone marrow environmental alterations underlie proliferative clonal expansion in clonal hematopoiesis2025