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Science. 2018 Aug 10;361(6402):594-599. doi: 10.1126/science.aat1699.

Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors.

Author information

1
Wellcome Sanger Institute, Hinxton CB10 1SA, UK.
2
Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
3
Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK.
4
UCL Division of Surgery and Interventional Science, Royal Free Hospital, London NW3 2PS, UK.
5
Specialist Centre for Kidney Cancer, Royal Free Hospital, London NW3 2PS, UK.
6
Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QQ, UK.
7
Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK.
8
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
9
Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
10
UCL Great Ormond Street Hospital Institute of Child Health, London WC1N 1E, UK.
11
Human Developmental Biology Resource, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
12
Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
13
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
14
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. sb31@sanger.ac.uk mrc38@medschl.cam.ac.uk st9@sanger.ac.uk m.a.haniffa@newcastle.ac.uk.
15
Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
16
Wellcome Sanger Institute, Hinxton CB10 1SA, UK. sb31@sanger.ac.uk mrc38@medschl.cam.ac.uk st9@sanger.ac.uk m.a.haniffa@newcastle.ac.uk.
17
Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK. sb31@sanger.ac.uk mrc38@medschl.cam.ac.uk st9@sanger.ac.uk m.a.haniffa@newcastle.ac.uk.

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.

PMID:
30093597
DOI:
10.1126/science.aat1699
[Indexed for MEDLINE]

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