Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps
Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic and therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic and imaging atlas of the two most common human col...
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| Format: | Article |
| Language: | English |
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Elsevier BV
2023
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| Online Access: | https://hdl.handle.net/1721.1/147095 |
| _version_ | 1826203119079391232 |
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| author | Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Regev, Aviv |
| author_sort | Regev, Aviv |
| collection | MIT |
| description | Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic and therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic and imaging atlas of the two most common human colorectal polyps, conventional adenomas and serrated polyps, and their resulting CRC counterparts. Integrative analysis of 128 datasets from 62 participants reveals adenomas arise from WNT-driven expansion of stem cells, while serrated polyps derive from differentiated cells through gastric metaplasia. Metaplasia-associated damage is coupled to a cytotoxic immune microenvironment preceding hypermutation, driven partly by antigen-presentation differences associated with tumor cell-differentiation status. Microsatellite unstable CRCs contain distinct non-metaplastic regions where tumor cells acquire stem cell properties and cytotoxic immune cells are depleted. Our multi-omic atlas provides insights into malignant progression of colorectal polyps and their microenvironment, serving as a framework for precision surveillance and prevention of CRC. |
| first_indexed | 2024-09-23T12:31:57Z |
| format | Article |
| id | mit-1721.1/147095 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:31:57Z |
| publishDate | 2023 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1470952023-01-14T03:25:28Z Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps Regev, Aviv Massachusetts Institute of Technology. Department of Biology Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic and therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic and imaging atlas of the two most common human colorectal polyps, conventional adenomas and serrated polyps, and their resulting CRC counterparts. Integrative analysis of 128 datasets from 62 participants reveals adenomas arise from WNT-driven expansion of stem cells, while serrated polyps derive from differentiated cells through gastric metaplasia. Metaplasia-associated damage is coupled to a cytotoxic immune microenvironment preceding hypermutation, driven partly by antigen-presentation differences associated with tumor cell-differentiation status. Microsatellite unstable CRCs contain distinct non-metaplastic regions where tumor cells acquire stem cell properties and cytotoxic immune cells are depleted. Our multi-omic atlas provides insights into malignant progression of colorectal polyps and their microenvironment, serving as a framework for precision surveillance and prevention of CRC. 2023-01-13T14:40:20Z 2023-01-13T14:40:20Z 2021 2023-01-13T14:11:41Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147095 Regev, Aviv. 2021. "Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps." Cell, 184 (26). en 10.1016/J.CELL.2021.11.031 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Regev, Aviv Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps |
| title | Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps |
| title_full | Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps |
| title_fullStr | Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps |
| title_full_unstemmed | Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps |
| title_short | Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps |
| title_sort | differential pre malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps |
| url | https://hdl.handle.net/1721.1/147095 |
| work_keys_str_mv | AT regevaviv differentialpremalignantprogramsandmicroenvironmentchartdistinctpathstomalignancyinhumancolorectalpolyps |