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Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma
Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10042888/ https://www.ncbi.nlm.nih.gov/pubmed/36973268 http://dx.doi.org/10.1038/s41467-023-37211-7 |
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author | Wu, Yige Terekhanova, Nadezhda V. Caravan, Wagma Naser Al Deen, Nataly Lal, Preet Chen, Siqi Mo, Chia-Kuei Cao, Song Li, Yize Karpova, Alla Liu, Ruiyang Zhao, Yanyan Shinkle, Andrew Strunilin, Ilya Weimholt, Cody Sato, Kazuhito Yao, Lijun Serasanambati, Mamatha Yang, Xiaolu Wyczalkowski, Matthew Zhu, Houxiang Zhou, Daniel Cui Jayasinghe, Reyka G. Mendez, Daniel Wendl, Michael C. Clark, David Newton, Chelsea Ruan, Yijun Reimers, Melissa A. Pachynski, Russell K. Kinsinger, Chris Jewell, Scott Chan, Daniel W. Zhang, Hui Chaudhuri, Aadel A. Chheda, Milan G. Humphreys, Benjamin D. Mesri, Mehdi Rodriguez, Henry Hsieh, James J. Ding, Li Chen, Feng |
author_facet | Wu, Yige Terekhanova, Nadezhda V. Caravan, Wagma Naser Al Deen, Nataly Lal, Preet Chen, Siqi Mo, Chia-Kuei Cao, Song Li, Yize Karpova, Alla Liu, Ruiyang Zhao, Yanyan Shinkle, Andrew Strunilin, Ilya Weimholt, Cody Sato, Kazuhito Yao, Lijun Serasanambati, Mamatha Yang, Xiaolu Wyczalkowski, Matthew Zhu, Houxiang Zhou, Daniel Cui Jayasinghe, Reyka G. Mendez, Daniel Wendl, Michael C. Clark, David Newton, Chelsea Ruan, Yijun Reimers, Melissa A. Pachynski, Russell K. Kinsinger, Chris Jewell, Scott Chan, Daniel W. Zhang, Hui Chaudhuri, Aadel A. Chheda, Milan G. Humphreys, Benjamin D. Mesri, Mehdi Rodriguez, Henry Hsieh, James J. Ding, Li Chen, Feng |
author_sort | Wu, Yige |
collection | PubMed |
description | Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor subpopulations. Finally, BAP1 mutations are associated with widespread reduction of chromatin accessibility, while PBRM1 mutations generally increase accessibility, with the former affecting five times more accessible peaks than the latter. These integrated analyses reveal the cellular architecture of ccRCC, providing insights into key markers and pathways in ccRCC tumorigenesis. |
format | Online Article Text |
id | pubmed-10042888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100428882023-03-29 Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma Wu, Yige Terekhanova, Nadezhda V. Caravan, Wagma Naser Al Deen, Nataly Lal, Preet Chen, Siqi Mo, Chia-Kuei Cao, Song Li, Yize Karpova, Alla Liu, Ruiyang Zhao, Yanyan Shinkle, Andrew Strunilin, Ilya Weimholt, Cody Sato, Kazuhito Yao, Lijun Serasanambati, Mamatha Yang, Xiaolu Wyczalkowski, Matthew Zhu, Houxiang Zhou, Daniel Cui Jayasinghe, Reyka G. Mendez, Daniel Wendl, Michael C. Clark, David Newton, Chelsea Ruan, Yijun Reimers, Melissa A. Pachynski, Russell K. Kinsinger, Chris Jewell, Scott Chan, Daniel W. Zhang, Hui Chaudhuri, Aadel A. Chheda, Milan G. Humphreys, Benjamin D. Mesri, Mehdi Rodriguez, Henry Hsieh, James J. Ding, Li Chen, Feng Nat Commun Article Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor subpopulations. Finally, BAP1 mutations are associated with widespread reduction of chromatin accessibility, while PBRM1 mutations generally increase accessibility, with the former affecting five times more accessible peaks than the latter. These integrated analyses reveal the cellular architecture of ccRCC, providing insights into key markers and pathways in ccRCC tumorigenesis. Nature Publishing Group UK 2023-03-27 /pmc/articles/PMC10042888/ /pubmed/36973268 http://dx.doi.org/10.1038/s41467-023-37211-7 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wu, Yige Terekhanova, Nadezhda V. Caravan, Wagma Naser Al Deen, Nataly Lal, Preet Chen, Siqi Mo, Chia-Kuei Cao, Song Li, Yize Karpova, Alla Liu, Ruiyang Zhao, Yanyan Shinkle, Andrew Strunilin, Ilya Weimholt, Cody Sato, Kazuhito Yao, Lijun Serasanambati, Mamatha Yang, Xiaolu Wyczalkowski, Matthew Zhu, Houxiang Zhou, Daniel Cui Jayasinghe, Reyka G. Mendez, Daniel Wendl, Michael C. Clark, David Newton, Chelsea Ruan, Yijun Reimers, Melissa A. Pachynski, Russell K. Kinsinger, Chris Jewell, Scott Chan, Daniel W. Zhang, Hui Chaudhuri, Aadel A. Chheda, Milan G. Humphreys, Benjamin D. Mesri, Mehdi Rodriguez, Henry Hsieh, James J. Ding, Li Chen, Feng Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma |
title | Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma |
title_full | Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma |
title_fullStr | Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma |
title_full_unstemmed | Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma |
title_short | Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma |
title_sort | epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10042888/ https://www.ncbi.nlm.nih.gov/pubmed/36973268 http://dx.doi.org/10.1038/s41467-023-37211-7 |
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