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An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution
Cancer cells’ ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2021
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990071/ https://www.ncbi.nlm.nih.gov/pubmed/34754079 http://dx.doi.org/10.1038/s41418-021-00895-9 |
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| author | Lindner, Andreas Ulrich Salvucci, Manuela McDonough, Elizabeth Cho, Sanghee Stachtea, Xanthi O’Connell, Emer P. Corwin, Alex D. Santamaria-Pang, Alberto Carberry, Steven Fichtner, Michael Van Schaeybroeck, Sandra Laurent-Puig, Pierre Burke, John P. McNamara, Deborah A. Lawler, Mark Sood, Anup Graf, John F. Rehm, Markus Dunne, Philip D. Longley, Daniel B. Ginty, Fiona Prehn, Jochen H. M. |
| author_facet | Lindner, Andreas Ulrich Salvucci, Manuela McDonough, Elizabeth Cho, Sanghee Stachtea, Xanthi O’Connell, Emer P. Corwin, Alex D. Santamaria-Pang, Alberto Carberry, Steven Fichtner, Michael Van Schaeybroeck, Sandra Laurent-Puig, Pierre Burke, John P. McNamara, Deborah A. Lawler, Mark Sood, Anup Graf, John F. Rehm, Markus Dunne, Philip D. Longley, Daniel B. Ginty, Fiona Prehn, Jochen H. M. |
| author_sort | Lindner, Andreas Ulrich |
| collection | PubMed |
| description | Cancer cells’ ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an enrichment for BCL2 in immune, and BAK, SMAC, and XIAP in cancer cells. Ordinary differential equation-based modeling of apoptosis sensitivity at single-cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. Systems modeling at single-cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, but showed significant inter- and intra-tumor heterogeneity. |
| format | Online Article Text |
| id | pubmed-8990071 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-89900712022-04-22 An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution Lindner, Andreas Ulrich Salvucci, Manuela McDonough, Elizabeth Cho, Sanghee Stachtea, Xanthi O’Connell, Emer P. Corwin, Alex D. Santamaria-Pang, Alberto Carberry, Steven Fichtner, Michael Van Schaeybroeck, Sandra Laurent-Puig, Pierre Burke, John P. McNamara, Deborah A. Lawler, Mark Sood, Anup Graf, John F. Rehm, Markus Dunne, Philip D. Longley, Daniel B. Ginty, Fiona Prehn, Jochen H. M. Cell Death Differ Article Cancer cells’ ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an enrichment for BCL2 in immune, and BAK, SMAC, and XIAP in cancer cells. Ordinary differential equation-based modeling of apoptosis sensitivity at single-cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. Systems modeling at single-cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, but showed significant inter- and intra-tumor heterogeneity. Nature Publishing Group UK 2021-11-09 2022-04 /pmc/articles/PMC8990071/ /pubmed/34754079 http://dx.doi.org/10.1038/s41418-021-00895-9 Text en © The Author(s) 2021 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 Lindner, Andreas Ulrich Salvucci, Manuela McDonough, Elizabeth Cho, Sanghee Stachtea, Xanthi O’Connell, Emer P. Corwin, Alex D. Santamaria-Pang, Alberto Carberry, Steven Fichtner, Michael Van Schaeybroeck, Sandra Laurent-Puig, Pierre Burke, John P. McNamara, Deborah A. Lawler, Mark Sood, Anup Graf, John F. Rehm, Markus Dunne, Philip D. Longley, Daniel B. Ginty, Fiona Prehn, Jochen H. M. An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution |
| title | An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution |
| title_full | An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution |
| title_fullStr | An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution |
| title_full_unstemmed | An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution |
| title_short | An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution |
| title_sort | atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990071/ https://www.ncbi.nlm.nih.gov/pubmed/34754079 http://dx.doi.org/10.1038/s41418-021-00895-9 |
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