Research Paper Volume 16, Issue 13 pp 10943—10971

Unfolding the mysteries of heterogeneity from a high-resolution perspective: integration analysis of single-cell multi-omics and spatial omics revealed functionally heterogeneous cancer cells in ccRCC

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Figure 1. The workflow of the presented study. In this study, we approached the functional heterogeneity of cancer cells from a single-cell multi-omics perspective, classifying them into metabolism, inflammatory, and EMT meta programs. Spatial transcriptome sequencing provided spatial information about these distinct meta programs within cancer cells. Bulk-RNA data revealed the high clinical prognostic value of the functional heterogeneity of cancer cells. Transcription factor regulatory networks and motif activities unveiled key transcription factors regulating the functional heterogeneity of ccRCC cancer cells. Interactions between different meta programs cancer cells and other cellular subpopulations in the tumor microenvironment were demonstrated using cellphoneDB. Finally, we assessed the sensitivity of cancer cells from different meta programs to various anticancer drugs.