Matthew D. Young, Thomas J. Mitchell, Felipe A. Vieira Braga, Maxine G.B. Tran, Benjamin J. Stewart, John R. Ferdinand, Grace Collord, Rachel A. Botting, Dorin Mirel Popescu, Kevin W. Loudon, Roser Vento-Tormo, Emily Stephenson, Alex Cagan, Sarah J. Farndon, Martin Del Castillo Velasco-Herrera, Charlotte Guzzo, Nathan Richoz, Lira Mamanova, Tevita Aho, James N. Armitage, Antony C.P. Riddick, Imran Mushtaq, Stephen Farrell, Dyanne Rampling, James Nicholson, Andrew Filby, Johanna Burge, Steven Lisgo, Patrick H. Maxwell, Susan Lindsay, Anne Y. Warren, Grant D. Stewart, Neil Sebire, Nicholas Coleman, Muzlifah Haniffa, Sarah A. Teichmann, Menna Clatworthy, Sam Behjati
Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors.