Clonal Hematopoiesis Drives Fibrotic Remodeling of the Bone Marrow Microenvironment [dataset 1]

Using single-cell transcriptomic and histologic profiling of freshly isolated human BM, we show that CHIP profoundly remodels the niche through fibroblast expansion and early fibrotic transformation. CHIP carriers exhibited myeloid-biased hematopoiesis, broad enrichment of inflammatory signaling, and metabolic reprogramming of CD4⁺ and CD8⁺ T cells, with CD8⁺ T cells emerging as key sources of TNFα.

Strikingly, fibroblast expansion occurred irrespective of mutational subtype and was characterized by transcriptional programs analogous to cancer-associated fibroblasts (CAFs). These cells demonstrated signaling interactions with hematopoietic and immune compartments through collagen-integrin adhesion pathways as well as IL-6 and TGFβ cytokine networks. Histologic validation confirmed reticulin and collagen deposition, establishing a pre-fibrotic niche state.