Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution
Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Elsevier BV
2022
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| Online Access: | https://hdl.handle.net/1721.1/146823 |
| _version_ | 1826207772775022592 |
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| author | Yang, Dian Jones, Matthew G Naranjo, Santiago Rideout, William M Min, Kyung Hoi Joseph Ho, Raymond Wu, Wei Replogle, Joseph M Page, Jennifer L Quinn, Jeffrey J Horns, Felix Qiu, Xiaojie Chen, Michael Z Freed-Pastor, William A McGinnis, Christopher S Patterson, David M Gartner, Zev J Chow, Eric D Bivona, Trever G Chan, Michelle M Yosef, Nir Jacks, Tyler Weissman, Jonathan S |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Yang, Dian Jones, Matthew G Naranjo, Santiago Rideout, William M Min, Kyung Hoi Joseph Ho, Raymond Wu, Wei Replogle, Joseph M Page, Jennifer L Quinn, Jeffrey J Horns, Felix Qiu, Xiaojie Chen, Michael Z Freed-Pastor, William A McGinnis, Christopher S Patterson, David M Gartner, Zev J Chow, Eric D Bivona, Trever G Chan, Michelle M Yosef, Nir Jacks, Tyler Weissman, Jonathan S |
| author_sort | Yang, Dian |
| collection | MIT |
| description | Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution. We found that the loss of the initial, stable alveolar-type2-like state was accompanied by a transient increase in plasticity. This was followed by the adoption of distinct transcriptional programs that enable rapid expansion and, ultimately, clonal sweep of stable subclones capable of metastasizing. Finally, tumors develop through stereotypical evolutionary trajectories, and perturbing additional tumor suppressors accelerates progression by creating novel trajectories. Our study elucidates the hierarchical nature of tumor evolution and, more broadly, enables in-depth studies of tumor progression. |
| first_indexed | 2024-09-23T13:54:43Z |
| format | Article |
| id | mit-1721.1/146823 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:54:43Z |
| publishDate | 2022 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1468232022-12-10T03:19:04Z Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution Yang, Dian Jones, Matthew G Naranjo, Santiago Rideout, William M Min, Kyung Hoi Joseph Ho, Raymond Wu, Wei Replogle, Joseph M Page, Jennifer L Quinn, Jeffrey J Horns, Felix Qiu, Xiaojie Chen, Michael Z Freed-Pastor, William A McGinnis, Christopher S Patterson, David M Gartner, Zev J Chow, Eric D Bivona, Trever G Chan, Michelle M Yosef, Nir Jacks, Tyler Weissman, Jonathan S Massachusetts Institute of Technology. Department of Biology Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution. We found that the loss of the initial, stable alveolar-type2-like state was accompanied by a transient increase in plasticity. This was followed by the adoption of distinct transcriptional programs that enable rapid expansion and, ultimately, clonal sweep of stable subclones capable of metastasizing. Finally, tumors develop through stereotypical evolutionary trajectories, and perturbing additional tumor suppressors accelerates progression by creating novel trajectories. Our study elucidates the hierarchical nature of tumor evolution and, more broadly, enables in-depth studies of tumor progression. 2022-12-09T18:58:23Z 2022-12-09T18:58:23Z 2022 2022-12-09T18:50:02Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146823 Yang, Dian, Jones, Matthew G, Naranjo, Santiago, Rideout, William M, Min, Kyung Hoi Joseph et al. 2022. "Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution." Cell, 185 (11). en 10.1016/J.CELL.2022.04.015 Cell Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Yang, Dian Jones, Matthew G Naranjo, Santiago Rideout, William M Min, Kyung Hoi Joseph Ho, Raymond Wu, Wei Replogle, Joseph M Page, Jennifer L Quinn, Jeffrey J Horns, Felix Qiu, Xiaojie Chen, Michael Z Freed-Pastor, William A McGinnis, Christopher S Patterson, David M Gartner, Zev J Chow, Eric D Bivona, Trever G Chan, Michelle M Yosef, Nir Jacks, Tyler Weissman, Jonathan S Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution |
| title | Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution |
| title_full | Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution |
| title_fullStr | Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution |
| title_full_unstemmed | Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution |
| title_short | Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution |
| title_sort | lineage tracing reveals the phylodynamics plasticity and paths of tumor evolution |
| url | https://hdl.handle.net/1721.1/146823 |
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