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.
Science (New York, N.Y.). 2018 Aug 10 [Epub]
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
Wellcome Sanger Institute, Hinxton CB10 1SA, UK., UCL Division of Surgery and Interventional Science, Royal Free Hospital, London NW3 2PS, UK., Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QQ, UK., Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK., Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK., Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK., Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK., Human Developmental Biology Resource, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK., Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK., Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. ., Wellcome Sanger Institute, Hinxton CB10 1SA, UK. ., Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK. .