The multiple myeloma microenvironment is defined by an inflammatory stromal cell landscape
Single-cell RNA sequencing datasets of the immune and non-hematopoietic bone marrow microenvironment and plasma cells of newly diagnosed individuals with multiple myeloma and non-cancer control patients as published by De Jong et al., Nat Immunol. 2021 Jun;22(6):769-780 doi: 10.1038/s41590-021-00931-3 Abstract: Progression and persistence of malignancies are influenced by the local tumor microenvironment, and future eradication of currently incurable tumors will, in part, hinge on our understanding of malignant cell biology in the context of their nourishing surroundings. Here, we generated paired single-cell transcriptomic datasets of tumor cells and the bone marrow immune and stromal microenvironment in multiple myeloma. These analyses identified myeloma-specific inflammatory mesenchymal stromal cells, which spatially colocalized with tumor cells and immune cells and transcribed genes involved in tumor survival and immune modulation. Inflammatory stromal cell signatures were driven by stimulation with proinflammatory cytokines, and analyses of immune cell subsets suggested interferon-responsive effector T cell and CD8+ stem cell memory T cell populations as potential sources of stromal cell-activating cytokines. Tracking stromal inflammation in individuals over time revealed that successful antitumor induction therapy is unable to revert bone marrow inflammation, predicting a role for mesenchymal stromal cells in disease persistence.
Steps to reproduce
Important notices The datasets are divided over two zip-files: 1) Nonhematopoietic_CD38neg.zip; this folder contains subfolders per patient as mentioned in the paper (see supplementary tables for patient characteristics). Within the subfolders are the filtered_feature_bc_matrix output directories for both the non-hematopoietic dataset, as well as the CD38neg hematopoietic dataset. These cells were combined in one 10x run to facilitate improved recovery. 2) CD38pos.zip: this folder contains subfolders per patient as mentioned in the paper (see supplementary tables for patient characteristics). Within the subfolders are the filtered_feature_bc_matrix output directories for the CD38pos hematopoietic dataset The non-hematopoietic and CD38neg datasets were separated using the subset() function and a list of barcodes of the non-hematopoietic cells. The barcodes and the scripts that were used to do this are available on our github page (https://github.com/MyelomaRotterdam/Microenvironment/blob/master/). NB: due to technical issues, one of the patients (PH2) has a separate CD38neg hematopoietic run. Therefore, the the hematopoietic cells in the nonhematopoietic_CD38neghematopoietic combined run of patient PH2 should not be used. The non-hematopoietic dataset uses a different set of controls than the hematopoietic datasets (again, see the supplementary tables in the paper). The hematopoietic cells in the nonhematopoietic_CD38neghematopoietic combined runs are random and should not be used for analysis. Rather, use the 5 separate control runs for hematopoietic datasets specifically (these have names like CBMx_CD38neg_only etc.) A basic script is included for R analyses. With any questions please contact us at firstname.lastname@example.org or email@example.com