Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer [scRNA-seq]

To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from polyps, normal tissues, and CRCs collected from patients with or without germline APC mutations. We find that a large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Nuclei from unaffected colon, polyps, and CRC samples were isolated with douncing. Following nuclei isolation, 10x scRNAseq and scATAC-seq assays were performed.