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Single cell derived mRNA signals across human kidney tumors.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Margaritis, Thanasis 
Morales-Rodriguez, Francisco 

Abstract

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.

Description

Keywords

Adult, Algorithms, Child, Fetus, Gene Expression Regulation, Developmental, Humans, Kidney, Kidney Neoplasms, Models, Genetic, RNA, Messenger, RNA-Seq, Signal Transduction, Single-Cell Analysis, Transcriptome

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

12

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Cancer Research UK (A25117)
Medical Research Council (MC_PC_17230)