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December 8, 2025BloodOpen Access

Tumor necrosis factor-alpha (TNFα) drives pathologic platelet hyperreactivity through signaling on hematopoietic stem/progenitor cells and expansion of canonical megakaryocytic progenitors.

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Authors

CLChristopher T. LetsonTGThomas GirardSOStephen T. Oh

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Overview

Chronic TNF-alpha influences platelet function in hematopoietic stem cells, suggesting new therapeutic targets.

Key Points

  • To elucidate the role of TNF-alpha signaling on megakaryocyte and hematopoietic stem cells in driving platelet hyperreactivity.
  • Developed a conditional knockout mouse model for megakaryocyte-specific TNF-alpha receptors.
  • Conducted single cell RNA sequencing on bone marrow cells from knockout and wildtype mice.
  • Performed adoptive transplantation of TNF-alpha receptor knockout HSPCs into irradiated mice.
  • Used multicolor flow cytometry to analyze megakaryocyte populations.
  • Chronic TNF-alpha treatment did not prevent the development of hyperreactive platelets in knockout mice.
  • Single cell RNA sequencing revealed low TNF-alpha receptor expression in megakaryocytes and progenitors.
  • Chronic exposure to TNF-alpha led to expansion of long-term and short-term hematopoietic stem cells.
  • Immunophenotyping confirmed expansion of myeloid biased HSPCs and canonical megakaryocytic progenitors.

Cite This Study

Letson et al. (2025) studied this question.

synapsesocial.com/papers/69362f4e4fa91c937236d8f0https://doi.org/10.1182/blood-2025-1250
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