Fig. 1

Overview of immune and stromal cell landscape in ccRCC bone metastasis. A Schematic illustration of experiment design and patient sample processing. B Sagittal T1 MRI imaging of the thoracic spine showing tumor masses with spinal cord compression for BM1 and BM9. C Integrative analysis of scRNA-seq samples of all bone marrow samples (Healthy, Benign, Involved, Distal, and Bone Met), visualized using a common UMAP embedding. D Bar plot representing the fraction of major cell types within each sample (column). E Dot plot representing key-marker gene expression in major cell types. The color represents scaled average expression of marker genes in each cell type, and the size indicates the proportion of cells expressing marker genes. F Integrative analysis of scRNA-seq samples from ccRCC primary and bone metastatic tumors, visualized using a common UMAP embedding for ccRCC primary samples (left), bone metastasis samples (right). G Comparison of relative cell abundance of major cell clusters between Bone Met (n = 9) and different control fractions (Healthy n = 12, Benign n = 7, Involved n = 4, Distal n = 4). Statistics are accessed with two-sided Wilcoxon rank sum test and BH multiple testing correction. (*p < 0.05, ***p < 0.001). H Pairwise expression distances between samples are shown using MDS embeddings. The similarity measures the magnitude of expression change for each subpopulation, using size-weighted average to combine them into an overall expression distance that controls the compositional differences. Each dot is a sample, with colors and point shapes corresponding to the sample condition. I UMAP embedding of joint alignment of the Benign bone marrow stromal cells, color coded by the cell type. J Heatmap of scaled normalized expression for representative marker gene expression in stromal cell populations