Fig. 5

Lung colonization bottleneck enriches for clonal populations with a common transcriptional phenotype. A Schematic of experimental set-up. B UMAP analysis of lineage-tagged OS-17 cells in culture, implanted into the tibia, or inoculated to generate lung-colonizing tumors. These lineage tags are heritable, allowing us to track the transcriptional profiles of daughter cells originating from the same ancestor. Lung- and tibia-colonizing tumor samples share many cells with similar phenotypes, though cultured cells are dramatically different (n = 2800 per condition). C Frequency distribution of clones identified in each of the conditions. A high level of clonal diversity is maintained in the tibia-colonizing tumors (78% unique clones in tibia-colonizing tumor compared to 86% unique clones in cell culture), while dominant clones emerge in the lung (only 33% unique clones). D Overlay of cells sharing a common ancestor onto the dimensional reduction plots in the top four enriched clonal families. E UMAP visualization of cells belonging to top ten enriched clonal families highlighted in red from the lung-colonizing tumor sample. F Pathway enrichment analysis for hallmark gene sets comparing enriched clones relative to the remaining lung-colonizing tumor cells identifies hypoxia, glycolysis, and EMT signaling-related genes to be significantly upregulated