Deciphering evolutional dynamics of resistance/recurrence-initiating singularity cells by RNA-expressed barcoding technology
Therapeutic resistance and recurrence are cancer evolutional dynamics that would be caused by an emergence of genetically and/or phenotypically distinct rare cancer cells. However, it has been totally unclear the molecular mechanism behind these singularity points of cancer malignant development. Here, we applied a novel RNA-expressed barcode technology (LARRY), which allows simultaneous lineage-tracing and transcriptome analysis at single cell resolution, and will develop a retrospective phenotype tracking method. in comjunction with Visium spatial transcriptome analysis, phenotypic trajectories of barcoded-cancer cells within tumor tissue undergoing to malignant development (e.g., therapeutic resistance to anti-PD-1). To establish such spatio-temporal methodology, we analyzed dynamics changes of spatial transcriptomics of cancer cells during a course of treatment with anti-PD-1 in D4M-UV2 mouse melanoma model. We expect to identify a previously unknown key cancer cell population that leads to the resistance to anti-PD-1 or other therapeutic agents by using the novel technology.