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Your search keyword '"Mamanova, Lira"' showing total 7 results
Start Over Author "Mamanova, Lira" Topic kidney neoplasms
7 results on '"Mamanova, Lira"'

1. Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer.

Author

Li R, Ferdinand JR, Loudon KW, Bowyer GS, Laidlaw S, Muyas F, Mamanova L, Neves JB, Bolt L, Fasouli ES, Lawson ARJ, Young MD, Hooks Y, Oliver TRW, Butler TM, Armitage JN, Aho T, Riddick ACP, Gnanapragasam V, Welsh SJ, Meyer KB, Warren AY, Tran MGB, Stewart GD, Cortés-Ciriano I, Behjati S, Clatworthy MR, Campbell PJ, Teichmann SA, and Mitchell TJ

Subjects
Humans, Transcriptome, Gene Expression Profiling, Epithelial-Mesenchymal Transition, Tumor Microenvironment genetics, Single-Cell Analysis, Carcinoma, Renal Cell genetics, Kidney Neoplasms genetics
Abstract

Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within the wider microenvironment, we studied over 270,000 single-cell transcriptomes and 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled from multiple regions of the tumor core, the tumor-normal interface, normal surrounding tissues, and peripheral blood. We find that the tissue-type location of CD8 + T cell clonotypes largely defines their exhaustion state with intra-tumoral spatial heterogeneity that is not well explained by somatic heterogeneity. De novo mutation calling from single-cell RNA-sequencing data allows us to broadly infer the clonality of stromal cells and lineage-trace myeloid cell development. We report six conserved meta-programs that distinguish tumor cell function, and find an epithelial-mesenchymal transition meta-program highly enriched at the tumor-normal interface that co-localizes with IL1B-expressing macrophages, offering a potential therapeutic target., Competing Interests: Declaration of interests In the past 3 years, S.A.T. has consulted for Roche and Genentech and is a Scientific Advisory Board member of Qiagen, Foresite labs, Biogen, and GSK, as well as a consultant and equity holder as co-founder of Transition Bio., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2022
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2. Single cell derived mRNA signals across human kidney tumors.

Author

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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3. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors.

Author

Young MD, Mitchell TJ, Vieira Braga FA, Tran MGB, Stewart BJ, Ferdinand JR, Collord G, Botting RA, Popescu DM, Loudon KW, Vento-Tormo R, Stephenson E, Cagan A, Farndon SJ, Del Castillo Velasco-Herrera M, Guzzo C, Richoz N, Mamanova L, Aho T, Armitage JN, Riddick ACP, Mushtaq I, Farrell S, Rampling D, Nicholson J, Filby A, Burge J, Lisgo S, Maxwell PH, Lindsay S, Warren AY, Stewart GD, Sebire N, Coleman N, Haniffa M, Teichmann SA, Clatworthy M, and Behjati S

Subjects
Adult, Carcinoma, Renal Cell classification, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell pathology, Child, Genetic Variation, Humans, Kidney embryology, Kidney Neoplasms classification, Single-Cell Analysis, Wilms Tumor classification, Wilms Tumor genetics, Wilms Tumor pathology, Kidney metabolism, Kidney Neoplasms genetics, Kidney Neoplasms pathology, Transcriptome
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., (Copyright © 2018, American Association for the Advancement of Science.)

Published
2018
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4. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors

Author

Young, Matthew D, Mitchell, Thomas J, Vieira Braga, Felipe A, Tran, Maxine GB, 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 CP, 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, and Behjati, Sam

Subjects
Adult, Genetic Variation, Humans, Single-Cell Analysis, Child, Kidney, Transcriptome, Carcinoma, Renal Cell, Wilms Tumor, Kidney Neoplasms, 3. Good health
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.

5. Single cell derived mRNA signals across human kidney tumors

Author

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

Subjects
Adult, Models, Genetic, Gene Expression Regulation, Developmental, Kidney, humanities, Kidney Neoplasms, 3. Good health, Fetus, Humans, RNA, Messenger, RNA-Seq, Single-Cell Analysis, Child, Transcriptome, Algorithms, Signal Transduction
Abstract

Funder: Department of Health, 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.

6. Single cell derived mRNA signals across human kidney tumors

Author

Eleonora Khabirova, Vincent J. Gnanapragasam, Tim H. H. Coorens, Adam Shlien, Nicholas Coleman, Omer Ali Bayraktar, Gerda Kildisiute, Muzlifah Haniffa, Federico Comitani, Roger A. Barker, Neil J. Sebire, Christine Thevanesan, Christina Burke, Kerstin B. Meyer, Stefan M. Pfister, Lars Custers, Dyanne Rampling, Karin Straathof, Elena Prigmore, Sarah A. Teichmann, Eva Bugallo-Blanco, Sam Behjati, Anne Y. Warren, Marry M. van den Heuvel-Eibrink, Thomas Rw Oliver, Ronald R. de Krijger, Ignacio del Valle, John Achermann, Anna Wilbrey-Clark, Kenny Roberts, Xiaoling He, Marcel Kool, Alice Piapi, Thanasis Margaritis, Jarno Drost, Felipe A. Vieira Braga, Kwasi Kwakwa, Kirsty Ambridge, Frank C. P. Holstege, Francisco Morales, Matthew D. Young, Thomas J. Mitchell, Grant D. Stewart, Liz Hook, Lira Mamanova, Young, Matthew D [0000-0003-0937-5290], Mitchell, Thomas J [0000-0003-0761-9503], Custers, Lars [0000-0003-0252-7714], Khabirova, Eleonora [0000-0002-5891-6789], Kildisiute, Gerda [0000-0002-5314-2294], Oliver, Thomas RW [0000-0003-4306-0102], van den Heuvel-Eibrink, Marry M [0000-0002-7760-879X], Comitani, Federico [0000-0003-3226-1179], Piapi, Alice [0000-0001-8251-3309], Burke, Christina [0000-0001-5381-3185], Roberts, Kenny [0000-0001-6155-0821], Coorens, Tim HH [0000-0002-5826-3554], Mamanova, Lira [0000-0003-1463-8622], Stewart, Grant D [0000-0003-3188-9140], Warren, Anne [0000-0002-1170-7867], Haniffa, Muzlifah [0000-0002-3927-2084], Achermann, John C [0000-0001-8787-6272], Bayraktar, Omer A [0000-0001-6055-277X], Teichmann, Sarah A [0000-0002-6294-6366], Holstege, Frank C [0000-0002-8090-5146], Meyer, Kerstin B [0000-0001-5906-1498], Drost, Jarno [0000-0002-2941-6179], Straathof, Karin [0000-0001-9673-8568], Behjati, Sam [0000-0002-6600-7665], Apollo - University of Cambridge Repository, Oliver, Thomas R W [0000-0003-4306-0102], Coorens, Tim H H [0000-0002-5826-3554], and Sebire, Neil [0000-0001-5348-9063]

Subjects
0301 basic medicine, Cell of origin, Cell, General Physics and Astronomy, Kidney, Transcriptome, 0302 clinical medicine, Gene expression, Cancer genomics, RNA-Seq, Child, Regulation of gene expression, 0303 health sciences, Multidisciplinary, Gene Expression Regulation, Developmental, Kidney Neoplasms, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Single-Cell Analysis, Algorithms, Signal Transduction, Adult, Science, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Fetus, medicine, Humans, RNA, Messenger, Transcriptomics, 030304 developmental biology, Messenger RNA, Models, Genetic, Mesenchymal stem cell, RNA, Kidney metabolism, Cancer, General Chemistry, medicine.disease, Clear cell renal cell carcinoma, 030104 developmental biology, Cancer research, 030217 neurology & neurosurgery
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., Transcriptomic analysis may provide information about the differentiation state and cell of origin of a cancer. Here, the authors assess mRNA signals in 1300 childhood and adult renal tumors and report a fetal origin of childhood tumors and no dedifferentiation of adult tumors.

Published
2020

7. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors

Author

Patrick H. Maxwell, Imran Mushtaq, Antony C. P. Riddick, Neil J. Sebire, Dyanne Rampling, Maxine G. B. Tran, Martin Del Castillo Velasco-Herrera, Steven Lisgo, John R. Ferdinand, Rachel A. Botting, Grant D. Stewart, Roser Vento-Tormo, Nicholas Coleman, Matthew D. Young, James Nicholson, Sarah J. Farndon, Menna R. Clatworthy, Charlotte Guzzo, James N. Armitage, Andrew Filby, Sam Behjati, Dorin-Mirel Popescu, Susan Lindsay, Sarah A. Teichmann, Lira Mamanova, Emily Stephenson, Anne Y. Warren, Alex Cagan, Nathan Richoz, Grace Collord, Muzlifah Haniffa, Thomas J. Mitchell, Stephen Farrell, Benjamin J. Stewart, Johanna Burge, Kevin W. Loudon, Felipe A. Vieira Braga, Tevita Aho, Young, Matthew D [0000-0003-0937-5290], Mitchell, Thomas J [0000-0003-0761-9503], Vieira Braga, Felipe A [0000-0003-0206-9258], Tran, Maxine GB [0000-0002-6034-4433], Stewart, Benjamin J [0000-0003-4522-0085], Ferdinand, John R [0000-0003-0936-0128], Collord, Grace [0000-0003-1924-4411], Stephenson, Emily [0000-0002-4244-4019], Farndon, Sarah J [0000-0001-6024-4267], Del Castillo Velasco-Herrera, Martin [0000-0001-5956-0211], Guzzo, Charlotte [0000-0003-3742-5961], Mamanova, Lira [0000-0003-1463-8622], Lisgo, Steven [0000-0001-5186-3971], Lindsay, Susan [0000-0003-2980-4582], Warren, Anne Y [0000-0002-1170-7867], Stewart, Grant D [0000-0003-3188-9140], Haniffa, Muzlifah [0000-0002-3927-2084], Teichmann, Sarah A [0000-0002-6294-6366], Clatworthy, Menna [0000-0002-3340-9828], Behjati, Sam [0000-0002-6600-7665], Apollo - University of Cambridge Repository, and Graduate School

Subjects
0301 basic medicine, Adult, Cell, Biology, Kidney, Wilms Tumor, Transcriptome, 03 medical and health sciences, chemistry.chemical_compound, Single-cell analysis, Renal cell carcinoma, medicine, Humans, Child, Carcinoma, Renal Cell, Multidisciplinary, Kidney metabolism, Cancer, Genetic Variation, Wilms' tumor, medicine.disease, Kidney Neoplasms, 3. Good health, Vascular endothelial growth factor, 030104 developmental biology, medicine.anatomical_structure, chemistry, Cancer research, Single-Cell Analysis
Abstract

Pediatric and adult kidney tumors differUnderstanding tumor origins and the similarities and differences between organ-specific cancers is important for determining treatment options. Younget al.generated more than 72,000 single-cell transcriptomes from healthy and cancerous human kidneys. From these data, they determined that Wilms tumor, a pediatric kidney cancer, originates from aberrant fetal cells, whereas adult kidney cancers are likely derived from a specific subtype of proximal convoluted tubular cell.Science, this issue p.594

Published
2018

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