Clonal hematopoiesis remodels human bone marrow into an inflammatory prefibrotic environment

In human bone marrow samples, researchers examined how clonal hematopoiesis of indeterminate potential reshapes the local tissue microenvironment. The team combined single-cell transcriptomic profiling of freshly isolated bone marrow cells with histological and spatial transcriptomic analyses. They found that fibro-inflammatory remodeling is a defining feature of the condition. Fibroblasts expanded markedly and shifted into cancer-associated fibroblast-like transcriptional states, while mesenchymal and vascular cells upregulated collagen production and extracellular matrix remodeling pathways. Spatial transcriptomics pinpointed discrete, fiber-rich niches populated by active and CXCL12-positive fibroblasts, macrophages, and lymphoid cells. These areas functioned as spatially confined inflammatory hubs, displaying strong enrichment of transforming growth factor-beta and tumor necrosis factor signaling pathways. The authors suggest this niche reorganization may facilitate progression to overt malignancy.