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December 8, 2025BloodOpen Access

Bone marrow environmental alterations underlie proliferative clonal expansion in clonal hematopoiesis

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Authors

RIRyosaku InagakiRSRyunosuke SaikiYOYotaro Ochi

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Overview

Single-cell analysis reveals altered gene expression and immune responses in clonal hematopoiesis, indicating a role for bone marrow microenvironment.

Key Points

  • To explore how bone marrow changes drive the selection and expansion of clones in age-related clonal hematopoiesis (CH).
  • Established a single-cell multi-omics platform to analyze hematopoietic stem and progenitor cells from CH(+) and CH(−) individuals.
  • Analyzed whole bone marrow cells with single-cell RNA sequencing to characterize the microenvironment.
  • Conducted competitive bone marrow transplantation assays in mice to evaluate the effects of mutant cells on wild-type cells.
  • Mutant hematopoietic stem and progenitor cells showed increased expression of proliferation-associated genes compared to wild-type.
  • CH(+) bone marrow exhibited altered immune composition, with increased T cells and decreased B cells.
  • Mutant clones influenced surrounding wild-type cells, altering their transcriptional state and enhancing interferon signaling.

Cite This Study

Inagaki et al. (2025) studied this question.

synapsesocial.com/papers/69362f364fa91c937236d2f7https://doi.org/10.1182/blood-2025-632
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