Single cell derived mRNA signals across human kidney tumors
Matthew D. Young, Thomas J. Mitchell, Lars Custers, Thanasis Margaritis, Francisco Morales-Rodriguez, Kwasi Kwakwa, Eleonora Khabirova, Gerda Kildisiute, Thomas R. W. Oliver, Ronald R. de Krijger, Marry M. van den Heuvel-Eibrink, Federico Comitani, Alice Piapi, Eva Bugallo-Blanco, Christine Thevanesan, Christina Burke, Elena Prigmore, Kirsty Ambridge, Kenny Roberts, Felipe A. Vieira Braga, Tim H. H. Coorens, Ignacio Del Valle, Anna Wilbrey-Clark, Lira Mamanova, Grant D. Stewart, Vincent J. Gnanapragasam, Dyanne Rampling, Neil Sebire, Nicholas Coleman, Liz Hook, Anne Warren, Muzlifah Haniffa, Marcel Kool, Stefan M. Pfister, John C. Achermann, Xiaoling He, Roger A. Barker, Adam Shlien, Omer A. Bayraktar, Sarah A. Teichmann, Frank C. Holstege, Kerstin B. Meyer, Jarno Drost, Karin Straathof, Sam Behjati
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.
Datasets
1. fetal
2. wilms
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Source data
https://cellxgene.cziscience.com/collections/13d1c580-4b17-4b2e-85c4-75b36917413f
Alias names
EGAD00001007498, PMID34162837, PMC8222373
Cite this study
Young, M.D., Mitchell, T.J., Custers, L., Margaritis, T., Morales-Rodriguez, F., Kwakwa, K., Khabirova, E., Kildisiute, G., Oliver, T.R., de Krijger, R.R. and van den Heuvel-Eibrink, M.M., 2021. Single cell derived mRNA signals across human kidney tumors. Nature Communications, 12(1), p.3896. https://doi.org/10.1038/s41467-021-23949-5