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A genome-wide single-cell 3D genome atlas of lung cancer progression
Alterations in three-dimensional (3D) genome structures are associated with cancer(1–5). However, how genome folding evolves and diversifies during subclonal cancer progression in the native tissue environment remains unknown. Here, we leveraged a genome-wide chromatin tracing technology to directly...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401964/ https://www.ncbi.nlm.nih.gov/pubmed/37546882 http://dx.doi.org/10.1101/2023.07.23.550157 |
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author | Liu, Miao Jin, Shengyan Agabiti, Sherry S. Jensen, Tyler B. Yang, Tianqi Radda, Jonathan S. D. Ruiz, Christian F. Baldissera, Gabriel Muzumdar, Mandar Deepak Wang, Siyuan |
author_facet | Liu, Miao Jin, Shengyan Agabiti, Sherry S. Jensen, Tyler B. Yang, Tianqi Radda, Jonathan S. D. Ruiz, Christian F. Baldissera, Gabriel Muzumdar, Mandar Deepak Wang, Siyuan |
author_sort | Liu, Miao |
collection | PubMed |
description | Alterations in three-dimensional (3D) genome structures are associated with cancer(1–5). However, how genome folding evolves and diversifies during subclonal cancer progression in the native tissue environment remains unknown. Here, we leveraged a genome-wide chromatin tracing technology to directly visualize 3D genome folding in situ in a faithful Kras-driven mouse model of lung adenocarcinoma (LUAD)(6), generating the first single-cell 3D genome atlas of any cancer. We discovered stereotypical 3D genome alterations during cancer development, including a striking structural bottleneck in preinvasive adenomas prior to progression to LUAD, indicating a stringent selection on the 3D genome early in cancer progression. We further showed that the 3D genome precisely encodes cancer states in single cells, despite considerable cell-to-cell heterogeneity. Finally, evolutionary changes in 3D genome compartmentalization – partially regulated by polycomb group protein Rnf2 through its ubiquitin ligase-independent activity – reveal novel genetic drivers and suppressors of LUAD progression. Our results demonstrate the importance of mapping the single-cell cancer 3D genome and the potential to identify new diagnostic and therapeutic biomarkers from 3D genomic architectures. |
format | Online Article Text |
id | pubmed-10401964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-104019642023-08-05 A genome-wide single-cell 3D genome atlas of lung cancer progression Liu, Miao Jin, Shengyan Agabiti, Sherry S. Jensen, Tyler B. Yang, Tianqi Radda, Jonathan S. D. Ruiz, Christian F. Baldissera, Gabriel Muzumdar, Mandar Deepak Wang, Siyuan bioRxiv Article Alterations in three-dimensional (3D) genome structures are associated with cancer(1–5). However, how genome folding evolves and diversifies during subclonal cancer progression in the native tissue environment remains unknown. Here, we leveraged a genome-wide chromatin tracing technology to directly visualize 3D genome folding in situ in a faithful Kras-driven mouse model of lung adenocarcinoma (LUAD)(6), generating the first single-cell 3D genome atlas of any cancer. We discovered stereotypical 3D genome alterations during cancer development, including a striking structural bottleneck in preinvasive adenomas prior to progression to LUAD, indicating a stringent selection on the 3D genome early in cancer progression. We further showed that the 3D genome precisely encodes cancer states in single cells, despite considerable cell-to-cell heterogeneity. Finally, evolutionary changes in 3D genome compartmentalization – partially regulated by polycomb group protein Rnf2 through its ubiquitin ligase-independent activity – reveal novel genetic drivers and suppressors of LUAD progression. Our results demonstrate the importance of mapping the single-cell cancer 3D genome and the potential to identify new diagnostic and therapeutic biomarkers from 3D genomic architectures. Cold Spring Harbor Laboratory 2023-07-24 /pmc/articles/PMC10401964/ /pubmed/37546882 http://dx.doi.org/10.1101/2023.07.23.550157 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Liu, Miao Jin, Shengyan Agabiti, Sherry S. Jensen, Tyler B. Yang, Tianqi Radda, Jonathan S. D. Ruiz, Christian F. Baldissera, Gabriel Muzumdar, Mandar Deepak Wang, Siyuan A genome-wide single-cell 3D genome atlas of lung cancer progression |
title | A genome-wide single-cell 3D genome atlas of lung cancer progression |
title_full | A genome-wide single-cell 3D genome atlas of lung cancer progression |
title_fullStr | A genome-wide single-cell 3D genome atlas of lung cancer progression |
title_full_unstemmed | A genome-wide single-cell 3D genome atlas of lung cancer progression |
title_short | A genome-wide single-cell 3D genome atlas of lung cancer progression |
title_sort | genome-wide single-cell 3d genome atlas of lung cancer progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401964/ https://www.ncbi.nlm.nih.gov/pubmed/37546882 http://dx.doi.org/10.1101/2023.07.23.550157 |
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