| First Author | Mistry JJ | Year | 2026 |
| Journal | Nat Cell Biol | Volume | 28 |
| Issue | 8 | Pages | 1656-1670 |
| PubMed ID | 42562925 | Mgi Jnum | J:392196 |
| Mgi Id | MGI:8406613 | Doi | 10.1038/s41556-026-02025-4 |
| Citation | Mistry JJ, et al. (2026) Stromal cell senescence augments haematopoietic cell fitness in clonal haematopoiesis. Nat Cell Biol 28(8):1656-1670 |
| abstractText | 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-alpha 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. |
