Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors
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 mat...
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Veröffentlicht in: | Science (American Association for the Advancement of Science) 2018-08, Vol.361 (6402), p.594-599 |
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creator | Young, Matthew D Mitchell, Thomas J Vieira Braga, Felipe A Tran, Maxine G B Stewart, Benjamin J Ferdinand, John R Collord, Grace Botting, Rachel A Popescu, Dorin-Mirel Loudon, Kevin W Vento-Tormo, Roser Stephenson, Emily Cagan, Alex Farndon, Sarah J Del Castillo Velasco-Herrera, Martin Guzzo, Charlotte Richoz, Nathan Mamanova, Lira Aho, Tevita Armitage, James N Riddick, Antony C P Mushtaq, Imran Farrell, Stephen Rampling, Dyanne Nicholson, James Filby, Andrew Burge, Johanna Lisgo, Steven Maxwell, Patrick H Lindsay, Susan Warren, Anne Y Stewart, Grant D Sebire, Neil Coleman, Nicholas Haniffa, Muzlifah Teichmann, Sarah A Clatworthy, Menna Behjati, Sam |
description | 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. |
doi_str_mv | 10.1126/science.aat1699 |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>ISSN: 1095-9203</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aat1699</identifier><identifier>PMID: 30093597</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Adult ; Cancer ; Carcinoma, Renal Cell - classification ; Carcinoma, Renal Cell - genetics ; Carcinoma, Renal Cell - pathology ; Child ; Children ; Composition ; Fetuses ; Gene expression ; Genetic Variation ; Growth factors ; Humans ; Kidney - embryology ; Kidney - metabolism ; Kidney cancer ; Kidney Neoplasms - classification ; Kidney Neoplasms - genetics ; Kidney Neoplasms - pathology ; Kidneys ; mRNA ; Pediatrics ; Phenotypes ; Renal cell carcinoma ; Ribonucleic acid ; RNA ; Single-Cell Analysis ; Transcriptome ; Tumor cells ; Tumors ; Vascular endothelial growth factor ; Wilms Tumor - classification ; Wilms Tumor - genetics ; Wilms Tumor - pathology</subject><ispartof>Science (American Association for the Advancement of Science), 2018-08, Vol.361 (6402), p.594-599</ispartof><rights>Copyright © 2018, American Association for the Advancement of Science.</rights><rights>Copyright © 2018, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-425f78cceccb32d77b8e41062074b08b46e73da279f1727782961b7ac88ae1da3</citedby><cites>FETCH-LOGICAL-c533t-425f78cceccb32d77b8e41062074b08b46e73da279f1727782961b7ac88ae1da3</cites><orcidid>0000-0003-1463-8622 ; 0000-0001-5186-3971 ; 0000-0002-3340-9828 ; 0000-0003-0761-9503 ; 0000-0003-1924-4411 ; 0000-0003-2980-4582 ; 0000-0003-3188-9140 ; 0000-0001-6024-4267 ; 0000-0003-3742-5961 ; 0000-0003-0206-9258 ; 0000-0001-5956-0211 ; 0000-0002-4244-4019 ; 0000-0003-0936-0128 ; 0000-0003-4522-0085 ; 0000-0002-6034-4433 ; 0000-0002-6294-6366 ; 0000-0002-3927-2084 ; 0000-0003-0937-5290 ; 0000-0002-1170-7867 ; 0000-0002-6600-7665</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,2871,2872,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30093597$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Young, Matthew D</creatorcontrib><creatorcontrib>Mitchell, Thomas J</creatorcontrib><creatorcontrib>Vieira Braga, Felipe A</creatorcontrib><creatorcontrib>Tran, Maxine G B</creatorcontrib><creatorcontrib>Stewart, Benjamin J</creatorcontrib><creatorcontrib>Ferdinand, John R</creatorcontrib><creatorcontrib>Collord, Grace</creatorcontrib><creatorcontrib>Botting, Rachel A</creatorcontrib><creatorcontrib>Popescu, Dorin-Mirel</creatorcontrib><creatorcontrib>Loudon, Kevin W</creatorcontrib><creatorcontrib>Vento-Tormo, Roser</creatorcontrib><creatorcontrib>Stephenson, Emily</creatorcontrib><creatorcontrib>Cagan, Alex</creatorcontrib><creatorcontrib>Farndon, Sarah J</creatorcontrib><creatorcontrib>Del Castillo Velasco-Herrera, Martin</creatorcontrib><creatorcontrib>Guzzo, Charlotte</creatorcontrib><creatorcontrib>Richoz, Nathan</creatorcontrib><creatorcontrib>Mamanova, Lira</creatorcontrib><creatorcontrib>Aho, Tevita</creatorcontrib><creatorcontrib>Armitage, James N</creatorcontrib><creatorcontrib>Riddick, Antony C P</creatorcontrib><creatorcontrib>Mushtaq, Imran</creatorcontrib><creatorcontrib>Farrell, Stephen</creatorcontrib><creatorcontrib>Rampling, Dyanne</creatorcontrib><creatorcontrib>Nicholson, James</creatorcontrib><creatorcontrib>Filby, Andrew</creatorcontrib><creatorcontrib>Burge, Johanna</creatorcontrib><creatorcontrib>Lisgo, Steven</creatorcontrib><creatorcontrib>Maxwell, Patrick H</creatorcontrib><creatorcontrib>Lindsay, Susan</creatorcontrib><creatorcontrib>Warren, Anne Y</creatorcontrib><creatorcontrib>Stewart, Grant D</creatorcontrib><creatorcontrib>Sebire, Neil</creatorcontrib><creatorcontrib>Coleman, Nicholas</creatorcontrib><creatorcontrib>Haniffa, Muzlifah</creatorcontrib><creatorcontrib>Teichmann, Sarah A</creatorcontrib><creatorcontrib>Clatworthy, Menna</creatorcontrib><creatorcontrib>Behjati, Sam</creatorcontrib><title>Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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.</description><subject>Adult</subject><subject>Cancer</subject><subject>Carcinoma, Renal Cell - classification</subject><subject>Carcinoma, Renal Cell - genetics</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Child</subject><subject>Children</subject><subject>Composition</subject><subject>Fetuses</subject><subject>Gene expression</subject><subject>Genetic Variation</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Kidney - embryology</subject><subject>Kidney - metabolism</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - classification</subject><subject>Kidney Neoplasms - genetics</subject><subject>Kidney Neoplasms - pathology</subject><subject>Kidneys</subject><subject>mRNA</subject><subject>Pediatrics</subject><subject>Phenotypes</subject><subject>Renal cell carcinoma</subject><subject>Ribonucleic 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titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Young, Matthew D</au><au>Mitchell, Thomas J</au><au>Vieira Braga, Felipe A</au><au>Tran, Maxine G B</au><au>Stewart, Benjamin J</au><au>Ferdinand, John R</au><au>Collord, Grace</au><au>Botting, Rachel A</au><au>Popescu, Dorin-Mirel</au><au>Loudon, Kevin W</au><au>Vento-Tormo, Roser</au><au>Stephenson, Emily</au><au>Cagan, Alex</au><au>Farndon, Sarah J</au><au>Del Castillo Velasco-Herrera, Martin</au><au>Guzzo, Charlotte</au><au>Richoz, Nathan</au><au>Mamanova, Lira</au><au>Aho, Tevita</au><au>Armitage, James N</au><au>Riddick, Antony C P</au><au>Mushtaq, Imran</au><au>Farrell, Stephen</au><au>Rampling, Dyanne</au><au>Nicholson, James</au><au>Filby, Andrew</au><au>Burge, Johanna</au><au>Lisgo, Steven</au><au>Maxwell, Patrick H</au><au>Lindsay, Susan</au><au>Warren, Anne Y</au><au>Stewart, Grant D</au><au>Sebire, Neil</au><au>Coleman, Nicholas</au><au>Haniffa, Muzlifah</au><au>Teichmann, Sarah A</au><au>Clatworthy, Menna</au><au>Behjati, Sam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2018-08-10</date><risdate>2018</risdate><volume>361</volume><issue>6402</issue><spage>594</spage><epage>599</epage><pages>594-599</pages><issn>0036-8075</issn><issn>1095-9203</issn><eissn>1095-9203</eissn><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.</abstract><cop>United States</cop><pub>The American Association for the Advancement of Science</pub><pmid>30093597</pmid><doi>10.1126/science.aat1699</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-1463-8622</orcidid><orcidid>https://orcid.org/0000-0001-5186-3971</orcidid><orcidid>https://orcid.org/0000-0002-3340-9828</orcidid><orcidid>https://orcid.org/0000-0003-0761-9503</orcidid><orcidid>https://orcid.org/0000-0003-1924-4411</orcidid><orcidid>https://orcid.org/0000-0003-2980-4582</orcidid><orcidid>https://orcid.org/0000-0003-3188-9140</orcidid><orcidid>https://orcid.org/0000-0001-6024-4267</orcidid><orcidid>https://orcid.org/0000-0003-3742-5961</orcidid><orcidid>https://orcid.org/0000-0003-0206-9258</orcidid><orcidid>https://orcid.org/0000-0001-5956-0211</orcidid><orcidid>https://orcid.org/0000-0002-4244-4019</orcidid><orcidid>https://orcid.org/0000-0003-0936-0128</orcidid><orcidid>https://orcid.org/0000-0003-4522-0085</orcidid><orcidid>https://orcid.org/0000-0002-6034-4433</orcidid><orcidid>https://orcid.org/0000-0002-6294-6366</orcidid><orcidid>https://orcid.org/0000-0002-3927-2084</orcidid><orcidid>https://orcid.org/0000-0003-0937-5290</orcidid><orcidid>https://orcid.org/0000-0002-1170-7867</orcidid><orcidid>https://orcid.org/0000-0002-6600-7665</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0036-8075 |
ispartof | Science (American Association for the Advancement of Science), 2018-08, Vol.361 (6402), p.594-599 |
issn | 0036-8075 1095-9203 1095-9203 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6104812 |
source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
subjects | Adult Cancer Carcinoma, Renal Cell - classification Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - pathology Child Children Composition Fetuses Gene expression Genetic Variation Growth factors Humans Kidney - embryology Kidney - metabolism Kidney cancer Kidney Neoplasms - classification Kidney Neoplasms - genetics Kidney Neoplasms - pathology Kidneys mRNA Pediatrics Phenotypes Renal cell carcinoma Ribonucleic acid RNA Single-Cell Analysis Transcriptome Tumor cells Tumors Vascular endothelial growth factor Wilms Tumor - classification Wilms Tumor - genetics Wilms Tumor - pathology |
title | Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors |
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