A proinflammatory response and polarized differentiation of stromal elements characterizes the murine myeloma bone marrow niche
To address the role of the non-hematopoietic bone marrow (BM) niche in multiple myeloma (MM) pathogenesis, we utilized the 5TGM1 murine model. During the asymptomatic precursor stage of the model, we isolated the rare non-hematopoietic cells and performed single-cell RNA sequencing. Using in-silico methods, we characterized the individual cellular components of the niche, their relative abundance, and differentation state both before and after exposure to MM cells, as well as their intercellular interactions. MM cells impact the BM niche by generating a pro-inflammatory microenvironment with MSC differentiation being changed away from osteocyte formation and towards adiopcytes, which helps to generate cell subsets that favor MM growth and survival. Overall design: KalwRij mice were injected with 5TGM1 murine MM cells and BM stromal cells were enriched by FACS sorting. 10x single-cell libraries were generated, pooled libraries were sequenced on a Novaseq 6000, and gene expression count matrices were generated using cellranger v5. Single-cell RNA analysis was performed in R using Seurat.