Single cell profiling of SW480 subtype-specific subcutaneous and orthotopic xenografts (SW480-CBC and SW480-RSC) as presented in "Colorectal Cancer Stem Cell Subtypes Orchestrate Distinct Tumor Microenvironments" [scRNA-seq]
Tumor heterogeneity derives from diverse populations of cancer cells that contribute unique properties to the microenvironment and tumor progression. While multiple classification systems have been developed to define tumor subtypes in colorectal cancer (CRC), the lack of single cell resolution has prohibited a better understanding of how these distinct cancer cell subtypes influence the overall tumor phenotype. Here were report that two cancer stem cell subtypes that are oncogenic versions of the intestinal Crypt Base Columnar (CBC) and Regenerative Stem Cell (RSC) populations, are commonly co-present in human CRC. We develop subtype-specific xenograft models utilizing a heterogeneous patient cell line (SW480) that contains CBCs and RSCs, and we define their tumor microenvironments at high resolution via single cell RNA sequencing. RSCs create differentiated, inflammatory, slow growing tumors. CBCs create proliferative, immune-suppressive, invasive tumors. With this enhanced resolution, we unify current CRC patient classification schema with TME phenotypes and organization. Overall design: SW480-subtype specific (CBC or RSC) and mixed parental SW480 xenograft tumors were generated in NSG mice by left and right rear flank injections (i.e. subcutaneous tumors; n=2 per subtype and SW480 parental) or by injecting cells into the submucosal space of the NSG mouse cecum (i.e. orthotopic tumors; n=4 per subtype only). Tumors developed for 21-28 days before excision and tissue dissociation for 10X Genomics single cell RNA-sequencing. "C2" and "pos" sample names refer to CBC xenografts; "E11" and "neg" sample names refer to RSC xenografts. We then performed Cell Ranger alignment and Seurat clustering to identify cells corresponding to the human tumor and mouse tumor microenvironment compartments. We provide compiled R objects (.rds) containing all of the mouse and human cells that passed quality control in subcutaneous tumors (subQ_xenografts combined) and orthotopic tumors (ortho_xenografts combined).