{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299122/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299122"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Stromal Cell Senescence Augments Hematopoietic Cell Fitness in Clonal Hematopoiesis","description":"Non-cell-autonomous mechanisms impact tumor growth and metastasis, including remodeling of the tissue microenvironment. The extent to which remodeling of the microenvironment 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 hematopoiesis, we identify subsets of mesenchymal stromal cells (MSCs) in a molecular state of cellular senescence. Using in vivo and ex vivo approaches, we find MSC senescence is induced by Dnmt3a-mutant hematopoietic cells in a cell contact-independent manner through soluble factors, including the cytokines IL-6 and TNF. Mechanistically, these cytokines activate a STAT3-driven senescence induction pathway selectively in MSCs and not in endothelial cells, underscoring cell context specificity. Depletion of senescent MSCs using genetic or pharmacological methods reduces the fitness of Dnmt3a-mutant hematopoietic stem and progenitor cells, and delays development of myeloproliferation which is a precursor to myeloid malignancy. Together, our work identifies that remodeling of the tissue microenvironment modifies pre-malignant clonal fitness and suggests disruption of the crosstalk between pre-malignant cells and their niche as a cancer prevention strategy.","dates":{"publication":"2026/05/14"},"accession":"GSE299122","cross_references":{"GSM":["GSM9033821","GSM9033820","GSM9033819","GSM9033825","GSM9033824","GSM9033823","GSM9033822","GSM9033829","GSM9033818","GSM9033828","GSM9033817","GSM9033827","GSM9033816","GSM9033826","GSM9033815"],"GPL":["24676"],"GSE":["299122"],"taxon":["Homo sapiens"]}}