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

doi:10.1038/s41467-021-23949-5

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 BragaTim 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

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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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.

Originele taal-2	Engels
Artikelnummer	3896
Pagina's (van-tot)	3896
Tijdschrift	Nature communications
Volume	12
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-021-23949-5
Status	Gepubliceerd - 23 jun. 2021

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Young, M. D., Mitchell, T. J., Custers, L., Margaritis, T., Morales-Rodriguez, F., Kwakwa, K., Khabirova, E., Kildisiute, G., Oliver, T. R. W., de Krijger, R. R., van den Heuvel-Eibrink, M. M., Comitani, F., Piapi, A., Bugallo-Blanco, E., Thevanesan, C., Burke, C., Prigmore, E., Ambridge, K., Roberts, K., ... Behjati, S. (2021). Single cell derived mRNA signals across human kidney tumors. Nature communications, 12(1), 3896. Artikel 3896. https://doi.org/10.1038/s41467-021-23949-5

@article{48b641b946c24ad79ac88fc9ba5841c9,

title = "Single cell derived mRNA signals across human kidney tumors",

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.",

keywords = "Adult, Algorithms, Child, Fetus/metabolism, Gene Expression Regulation, Developmental, Humans, Kidney/embryology, Kidney Neoplasms/embryology, Models, Genetic, RNA, Messenger/genetics, RNA-Seq/methods, Signal Transduction/genetics, Single-Cell Analysis/methods, Transcriptome",

author = "Young, {Matthew D} and Mitchell, {Thomas J} and Lars Custers and Thanasis Margaritis and Francisco Morales-Rodriguez and Kwasi Kwakwa and Eleonora Khabirova and Gerda Kildisiute and Oliver, {Thomas R W} and {de Krijger}, {Ronald R} and {van den Heuvel-Eibrink}, {Marry M} and Federico Comitani and Alice Piapi and Eva Bugallo-Blanco and Christine Thevanesan and Christina Burke and Elena Prigmore and Kirsty Ambridge and Kenny Roberts and Braga, {Felipe A Vieira} and Coorens, {Tim H H} and {Del Valle}, Ignacio and Anna Wilbrey-Clark and Lira Mamanova and Stewart, {Grant D} and Gnanapragasam, {Vincent J} and Dyanne Rampling and Neil Sebire and Nicholas Coleman and Liz Hook and Anne Warren and Muzlifah Haniffa and Marcel Kool and Pfister, {Stefan M} and Achermann, {John C} and Xiaoling He and Barker, {Roger A} and Adam Shlien and Bayraktar, {Omer A} and Teichmann, {Sarah A} and Holstege, {Frank C} and Meyer, {Kerstin B} and Jarno Drost and Karin Straathof and Sam Behjati",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = jun,

day = "23",

doi = "10.1038/s41467-021-23949-5",

language = "English",

volume = "12",

pages = "3896",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

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 & Behjati, S 2021, 'Single cell derived mRNA signals across human kidney tumors', Nature communications, vol. 12, nr. 1, 3896, blz. 3896. https://doi.org/10.1038/s41467-021-23949-5

TY - JOUR

T1 - Single cell derived mRNA signals across human kidney tumors

AU - Young, Matthew D

AU - Mitchell, Thomas J

AU - Custers, Lars

AU - Margaritis, Thanasis

AU - Morales-Rodriguez, Francisco

AU - Kwakwa, Kwasi

AU - Khabirova, Eleonora

AU - Kildisiute, Gerda

AU - Oliver, Thomas R W

AU - de Krijger, Ronald R

AU - van den Heuvel-Eibrink, Marry M

AU - Comitani, Federico

AU - Piapi, Alice

AU - Bugallo-Blanco, Eva

AU - Thevanesan, Christine

AU - Burke, Christina

AU - Prigmore, Elena

AU - Ambridge, Kirsty

AU - Roberts, Kenny

AU - Braga, Felipe A Vieira

AU - Coorens, Tim H H

AU - Del Valle, Ignacio

AU - Wilbrey-Clark, Anna

AU - Mamanova, Lira

AU - Stewart, Grant D

AU - Gnanapragasam, Vincent J

AU - Rampling, Dyanne

AU - Sebire, Neil

AU - Coleman, Nicholas

AU - Hook, Liz

AU - Warren, Anne

AU - Haniffa, Muzlifah

AU - Kool, Marcel

AU - Pfister, Stefan M

AU - Achermann, John C

AU - He, Xiaoling

AU - Barker, Roger A

AU - Shlien, Adam

AU - Bayraktar, Omer A

AU - Teichmann, Sarah A

AU - Holstege, Frank C

AU - Meyer, Kerstin B

AU - Drost, Jarno

AU - Straathof, Karin

AU - Behjati, Sam

PY - 2021/6/23

Y1 - 2021/6/23

N2 - 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.

AB - 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.

KW - Adult

KW - Algorithms

KW - Child

KW - Fetus/metabolism

KW - Gene Expression Regulation, Developmental

KW - Humans

KW - Kidney/embryology

KW - Kidney Neoplasms/embryology

KW - Models, Genetic

KW - RNA, Messenger/genetics

KW - RNA-Seq/methods

KW - Signal Transduction/genetics

KW - Single-Cell Analysis/methods

KW - Transcriptome

U2 - 10.1038/s41467-021-23949-5

DO - 10.1038/s41467-021-23949-5

M3 - Article

C2 - 34162837

SN - 2041-1723

VL - 12

SP - 3896

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3896

ER -

Single cell derived mRNA signals across human kidney tumors

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