Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors
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
Abstract
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.
Datasets
1. mature
Metadata
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4602STDY69491854876 cells 4602STDY69491844036 cells CZIKidney76328033016 cells CZIKidney76328042744 cells 4602STDY69491862135 cells 4602STDY70189232052 cells 4602STDY69491881788 cells 4602STDY69308531689 cells 4602STDY69308521602 cells 4602STDY69491871436 cells 4602STDY69764281114 cells 4602STDY69764271079 cells 4602STDY69764261076 cells 4602STDY69491921073 cells CZIKidney7587406501 cells CZIKidney7587408430 cells CZIKidney7587407422 cells CZIKidney7587405325 cells CZIKidney7587422101 cells Experiment set 132309 cells Experiment set 27959 cells Proximal tubule28061 cells Peritubular capillary endothelium851 cells Intercalated cell829 cells Thick ascending limb of Loop of Henle675 cells Glomerular endothelium622 cells MNP-a/classical monocyte derived555 cells MNP-b/non-classical monocyte derived375 cells Ascending vasa recta endothelium300 cells Epithelial progenitor cell238 cells MNP-c/dendritic cell220 cells Descending vasa recta endothelium192 cells Connecting tubule157 cells Pelvic epithelium136 cells MNP-d/Tissue macrophage87 cells Transitional urothelium45 cells Plasmacytoid dendritic cell23 cells Proximal tubule27497 cells Thick ascending limb of Loop of Henle675 cells Peritubular capillary endothelium 1666 cells Glomerular endothelium622 cells MNP-a/classical monocyte derived555 cells Indistinct intercalated cell429 cells MNP-b/non-classical monocyte derived375 cells Proliferating Proximal Tubule348 cells Ascending vasa recta endothelium300 cells Type A intercalated cell275 cells Epithelial progenitor cell238 cells MNP-c/dendritic cell220 cells Descending vasa recta endothelium192 cells Peritubular capillary endothelium 2185 cells Connecting tubule157 cells Distinct proximal tubule 2151 cells Pelvic epithelium136 cells Type B intercalated cell125 cells MNP-d/Tissue macrophage87 cells Distinct proximal tubule 165 cells Transitional urothelium45 cells Plasmacytoid dendritic cell23 cells HsapDv:000010615065 cells UBERON:000122520540 cells UBERON:000211314333 cells NCBITaxon:960640268 cells TeenTx left_Cortex left8912 cells TeenTx left_Medulla left3224 cells TeenTx right_Cortex right2135 cells TeenTx right_Medulla right794 cells Wilms3_ArteryVein46 cells epithelial cell of proximal tubule28061 cells CD4-positive, alpha-beta T cell2435 cells natural killer cell1322 cells mononuclear phagocyte1237 cells CD8-positive, alpha-beta T cell991 cells peritubular capillary endothelial cell851 cells kidney loop of Henle thick ascending limb epithelial cell675 cells glomerular endothelial cell622 cells renal intercalated cell429 cells vasa recta ascending limb cell300 cells renal alpha-intercalated cell275 cells vasa recta descending limb cell192 cells kidney connecting tubule epithelial cell157 cells kidney epithelial cell136 cells epithelial cell of glomerular capsule126 cells renal beta-intercalated cell125 cells myofibroblast cell122 cells renal principal cell88 cells plasmacytoid dendritic cell23 cells cortex of kidney20540 cells kidney blood vessel48 cells 12-year-old human stage15065 cells 72-year-old human stage8070 cells 67-year-old human stage3546 cells 63-year-old human stage3269 cells 49-year-old human stage3231 cells 2-year-old human stage2325 cells 4-year-old human stage1948 cells 53-year-old human stage1678 cells 19-month-old human stage586 cells 64-year-old human stage324 cells 44-year-old human stage164 cells 70-year-old human stage62 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/125eef58-0f61-4963-9b08-53e851ab65fb
Alias names
EGAS00001002325, PMID30093597, PMC6104812
Cite this study
Young, M.D., Mitchell, T.J., Vieira Braga, F.A., Tran, M.G., Stewart, B.J., Ferdinand, J.R., Collord, G., Botting, R.A., Popescu, D.M., Loudon, K.W. and Vento-Tormo, R., 2018. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors. science, 361(6402), pp.594-599. https://doi.org/10.1126/science.aat1699
