Nature cell biologyAug 7, 2026

Aging support cells improve blood cell health in clonal blood growth

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 9, 2026

Abstract

Elevated bone-marrow mesenchymal stromal cell (MSC) senescence is observed in humans with clonal haematopoiesis (CH) driven by common somatic mutations.

Microenvironment remodelling may influence the growth and spread of tumors by impacting the fitness of pre-malignant clones.
Single-cell RNA-sequencing in a mouse model reveals that MSCs are in a state of cellular senescence due to interactions with mutant haematopoietic cells.
Contact-independent factors, such as TNF-α and IL-6 produced by mutant cells, are associated with inducing MSC senescence.
Activation of a specific pathway driven by Stat3 is necessary for the induction of MSC senescence.
Reducing senescent non-haematopoietic cells through genetic or pharmacological means may lower the burden of CH and slow the onset of myeloid neoplasia.

Simplified

Microenvironment remodelling impacts tumour growth and metastasis, but whether remodelling promotes pre-malignant clonal fitness remains unknown. Here, using single-cell RNA-sequencing of the bone-marrow microenvironment in a mouse model of DNMT3A-mutant clonal haematopoiesis (CH), we identify mesenchymal stromal cells (MSCs) in a molecular state of cellular senescence. Elevated bone-marrow MSC senescence is also observed in humans with CH driven by several common somatic mutations. MSC senescence is induced by mutant haematopoietic cells in a contact-independent manner through production of soluble factors including TNF-α and IL-6. These cytokines activate a Stat3-driven pathway that is necessary and sufficient for MSC senescence induction. Genetic or pharmacological depletion of senescent non-haematopoietic cells reduces the burden of CH and delays progression to myeloid neoplasia. Our findings show that microenvironment remodelling modifies pre-malignant clonal fitness and identifies disruption of the crosstalk between pre-malignant cells and their niche as a cancer prevention strategy.