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

Accepted version
Peer-reviewed

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Article

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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.

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Keywords

Adult, Carcinoma, Renal Cell, Child, Genetic Variation, Humans, Kidney, Kidney Neoplasms, Single-Cell Analysis, Transcriptome, Wilms Tumor

Journal Title

Science

Conference Name

Journal ISSN

0036-8075
1095-9203

Volume Title

361

Publisher

American Association for the Advancement of Science (AAAS)
Sponsorship
Wellcome Trust (096956/Z/11/Z)
Medical Research Council (MR/M008975/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0514-10122)
Medical Research Council (MR/K023934/1)
Wellcome Trust (200110/Z/15/Z)
Medical Research Council (MR/N024907/1)
Arthritis Research UK (21777)