Tools
ToolsMistry, Jayna J., Young, Kira A., Navarro Figueredo, Anna, Edun, Gibran, Aguilar-Navarro, Alicia G., Colom Díaz, Patricia A., Telpoukhovskaia, Maria, Fernández Maestre, Inés, Cai, Sheng F., Götze, Katharina S., Tikhonova, Anastasia N., Levine, Ross L. and Trowbridge, Jennifer J. (2026) Stromal cell senescence augments haematopoietic cell fitness in clonal haematopoiesis. Nature Cell Biology, 28 (8). pp. 1656-1670. ISSN 1465-7392
Preview |
PDF (s41556-026-02025-4)
- Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (18MB) | Preview |
Abstract
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.
| Item Type: | Article |
|---|---|
| Additional Information: | Data availability: All data supporting the findings in this study are available within the Article, Supplementary tables and source data files. Sequencing data that support the findings of this study have been deposited in the Gene Expression Omnibus (GEO) under accession codes GSE240686 (mouse scRNA-seq data shown in Fig. 1) and GSE299122 (human bulk RNA-seq data shown in Fig. 3e–g), and the source data for human MSC scRNA-seq shown in Fig. 1g,h are provided in the source data file for Fig. 1. All other data supporting the findings of this study are available from the corresponding author on reasonable request. Source data are provided with this paper. |
| Uncontrolled Keywords: | cell biology,sdg 3 - good health and well-being,das in place,data availability all data supporting the findings in this study are available within the article, supplementary tables and source data files. sequencing data that support the findings of this study have been deposited in the gene expression omnibus (geo) under accession codes gse240686 (mouse scrna-seq data shown in fig. 1) and gse299122 (human bulk rna-seq data shown in fig. 3e–g), and the source data for human msc scrna-seq shown in fig. 1g,h are provided in the source data file for fig. 1. all other data supporting the findings of this study are available from the corresponding author on reasonable request. source data are provided with this paper.,2026 ,/dk/atira/pure/subjectarea/asjc/1300/1307 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 29 Oct 2026 15:09 |
| Last Modified: | 29 Oct 2026 15:09 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/104915 |
| DOI: | 10.1038/s41556-026-02025-4 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |