Single Cell Analyses of Renal Cell Cancers Reveal Insights into Tumor Microenvironment, Cell of Origin, and Therapy Response

ABSTRACT: Diverse subtypes of renal cell carcinomas (RCC) display a wide spectrum of histomorphologies, proteogenomic alterations, immune cell infiltration patterns, and clinical behavior. Delineating the ontogeny of these malignancies with the identification of cells of origin for different RCC subtypes will provide mechanistic insights into their diverse pathobiology. With this aim, we performed single cell RNA sequencing (scRNA-seq) analysis of ~30,000 cells dissociated from benign human kidney and renal tumor specimens. The benign renal tissue cell atlas comprised 26 distinct cell clusters representing all known major and minor cell types, as well as two rare proximal tubule cell types (PT-B and PT-C) and one novel entity containing both intercalated and principal cell (IC-PC) phenotypes. In comparison, the tumor cell atlas was comprised of 13 different cell clusters encompassing neoplastic cells and components of the tumor microenvironment. Using a random forest model trained on the scRNA-seq data from benign tubular epithelial cell types, we predicted the putative cell of origin for more than 10 different RCC subtypes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159115 | GEO | 2021/05/22

REPOSITORIES: GEO