1. Single cell derived mRNA signals across human kidney tumors.
- Author
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Young MD, Mitchell TJ, Custers L, Margaritis T, Morales-Rodriguez F, Kwakwa K, Khabirova E, Kildisiute G, Oliver TRW, de Krijger RR, van den Heuvel-Eibrink MM, Comitani F, Piapi A, Bugallo-Blanco E, Thevanesan C, Burke C, Prigmore E, Ambridge K, Roberts K, Braga FAV, Coorens THH, Del Valle I, Wilbrey-Clark A, Mamanova L, Stewart GD, Gnanapragasam VJ, Rampling D, Sebire N, Coleman N, Hook L, Warren A, Haniffa M, Kool M, Pfister SM, Achermann JC, He X, Barker RA, Shlien A, Bayraktar OA, Teichmann SA, Holstege FC, Meyer KB, Drost J, Straathof K, and Behjati S
- Subjects
- Adult, Algorithms, Child, Fetus metabolism, Gene Expression Regulation, Developmental, Humans, Kidney embryology, Kidney Neoplasms embryology, Kidney Neoplasms metabolism, Models, Genetic, Signal Transduction genetics, Kidney metabolism, Kidney Neoplasms genetics, RNA, Messenger genetics, RNA-Seq methods, Single-Cell Analysis methods, Transcriptome
- 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.
- Published
- 2021
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