Clonal Hematopoiesis Drives Fibrotic Remodeling of the Bone Marrow Microenvironment [dataset 2]

Using single-cell transcriptomic profiling of freshly isolated BM, we identify fibro-inflammatory remodeling as an early hallmark of CHIP. Beyond the established myeloid-biased inflammatory state, CHIP BM displayed coordinated TNFα activation spanning hematopoietic progenitors, monocytes, and stromal cells.

Stromal populations showed early fibrotic remodeling, with mesenchymal and vascular cells upregulating collagen and extracellular matrix gene programs. Fibroblasts were markedly expanded regardless of mutational subtype and acquired cancer-associated fibroblast (CAF)-like transcriptional states. Histological analysis confirmed the presence of pre-fibrotic stromal remodeling in CHIP BM, representing an early and potentially disease-defining pathological change.