Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics
The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2023-06-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI169653 |
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| author | Lina Lu Jennifer Rui Wang Ying C. Henderson Shanshan Bai Jie Yang Min Hu Cheng-Kai Shiau Timothy Pan Yuanqing Yan Tuan M. Tran Jianzhuo Li Rachel Kieser Xiao Zhao Jiping Wang Roza Nurieva Michelle D. Williams Maria E. Cabanillas Ramona Dadu Naifa Lamki Busaidy Mark Zafereo Nicholas Navin Stephen Y. Lai Ruli Gao |
| author_facet | Lina Lu Jennifer Rui Wang Ying C. Henderson Shanshan Bai Jie Yang Min Hu Cheng-Kai Shiau Timothy Pan Yuanqing Yan Tuan M. Tran Jianzhuo Li Rachel Kieser Xiao Zhao Jiping Wang Roza Nurieva Michelle D. Williams Maria E. Cabanillas Ramona Dadu Naifa Lamki Busaidy Mark Zafereo Nicholas Navin Stephen Y. Lai Ruli Gao |
| author_sort | Lina Lu |
| collection | DOAJ |
| description | The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC. |
| first_indexed | 2024-03-11T12:08:25Z |
| format | Article |
| id | doaj.art-0d8eae2e1a504a25ac0667fae8df590b |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:08:25Z |
| publishDate | 2023-06-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-0d8eae2e1a504a25ac0667fae8df590b2023-11-07T16:20:25ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-06-0113311Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomicsLina LuJennifer Rui WangYing C. HendersonShanshan BaiJie YangMin HuCheng-Kai ShiauTimothy PanYuanqing YanTuan M. TranJianzhuo LiRachel KieserXiao ZhaoJiping WangRoza NurievaMichelle D. WilliamsMaria E. CabanillasRamona DaduNaifa Lamki BusaidyMark ZafereoNicholas NavinStephen Y. LaiRuli GaoThe deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC.https://doi.org/10.1172/JCI169653GeneticsOncology |
| spellingShingle | Lina Lu Jennifer Rui Wang Ying C. Henderson Shanshan Bai Jie Yang Min Hu Cheng-Kai Shiau Timothy Pan Yuanqing Yan Tuan M. Tran Jianzhuo Li Rachel Kieser Xiao Zhao Jiping Wang Roza Nurieva Michelle D. Williams Maria E. Cabanillas Ramona Dadu Naifa Lamki Busaidy Mark Zafereo Nicholas Navin Stephen Y. Lai Ruli Gao Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics The Journal of Clinical Investigation Genetics Oncology |
| title | Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics |
| title_full | Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics |
| title_fullStr | Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics |
| title_full_unstemmed | Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics |
| title_short | Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics |
| title_sort | anaplastic transformation in thyroid cancer revealed by single cell transcriptomics |
| topic | Genetics Oncology |
| url | https://doi.org/10.1172/JCI169653 |
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