Fig. 2

Cellular ecosystem of the BM of MM patients. A Clinical data and single-cell profiles of MM patients. Cell counts indicate the single-cell transcriptome that passed the quality threshold for each patient. The proportions of malignant plasma cells detected in smears, flow cytometry, and scRNA-seq in BM aspirates for each patient are demonstrated in pie charts. The two pie charts for scRNA-seq in CD20⁺ RRMM patients represent the proportion of CD20⁺ malignant plasma cells and the proportion of all malignant plasma cells, respectively. B-D Identification of malignant plasma cells in patients with NDMM (B), RRMM (C), and CD20⁺ RRMM (D). Left: Single-cell atlas of t-SNE-visualized malignant cells of the microenvironment in patients. Top right: Identification of malignant plasma cells with clinical and laboratory markers of MM malignancy such as CD38, CD56 (NCAM1), CD138 (SDC1), and CD20. Bottom right: Flow cytometry plot for validation of malignant plasma cell identification. E Malignant plasma cell subpopulations in patients with MM. Left: t-SNE single-cell atlas visualizing malignant plasma cell subpopulations in the BM of patients with NDMM and RRMM. The top panel shows the cell cycle score and stemness score of these malignant plasma cell subpopulations. Right: t-SNE single-cell atlas visualizing malignant plasma cell subpopulations in CD20⁺ RRMM patients. F Malignant marker genes shared by malignant plasma cell subpopulations in patients with NDMM and RRMM. Cluster modules in columns indicate malignant plasma cell subpopulations, while rows indicate expression of marker genes, cell abundance, and cell ratio are also shown. G Specific expressed marker genes for malignant plasma cell sub-clusters. H Microenvironment cells in the BM of patients with MM. A single-cell atlas based on t-SNE showing cells in the microenvironment in NDMM, RRMM (left), and CD20⁺ RRMM (right). I Expression patterns of known cell identity-specific markers in MM patient myeloid tumor microenvironment cells. Relevant marker genes were specifically expressed in the corresponding cell identity. J High-confidence communication network between malignant plasma cells and cells of the microenvironment in the BM of patients with MM. The Circos plot demonstrates each high-confidence ligand-receptor interaction pair of malignant plasma cell subpopulations and microenvironmental cells. The arrowheads are oriented from the ligand of the source cell toward the receptor of the target cell, while the thickness of the arrowheads represents the mean value of expression of the ligand-receptor interaction pair. NDMM, newly diagnosed multiple myeloma; RRMM, refractory or recurrent multiple myeloma; t-SNE, t-distributed stochastic neighbor embedding; BM, bone marrow