دورية أكاديمية
Temporal chromatin accessibility changes define transcriptional states essential for osteosarcoma metastasis
| العنوان: | Temporal chromatin accessibility changes define transcriptional states essential for osteosarcoma metastasis |
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| المؤلفون: | Pontius, W. Dean, Hong, Ellen S., Faber, Zachary J., Gray, Jeremy, Peacock, Craig D., Bayles, Ian, Lovrenert, Katreya, Chin, Diana H., Gryder, Berkley E., Bartels, Cynthia F., Scacheri, Peter C. |
| المساهمون: | U.S. Department of Health & Human Services | NIH | National Cancer Institute, U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | The metastasis-invasion cascade describes the series of steps required for a cancer cell to successfully spread from its primary tumor and ultimately grow within a secondary organ. Despite metastasis being a dynamic, multistep process, most omics studies to date have focused on comparing primary tumors to the metastatic deposits that define end-stage disease. This static approach means we lack information about the genomic and epigenomic changes that occur during the majority of tumor progression. One particularly understudied phase of tumor progression is metastatic colonization, during which cells must adapt to the new microenvironment of the secondary organ. Through temporal profiling of chromatin accessibility and gene expression in vivo, we identify dynamic changes in the epigenome that occur as osteosarcoma tumors form and grow within the lung microenvironment. Furthermore, we show through paired in vivo and in vitro CRISPR drop-out screens and pharmacological validation that the upstream transcription factors represent a class of metastasis-specific dependency genes. While current models depict lung colonization as a discrete step within the metastatic cascade, our study shows it is a defined trajectory through multiple epigenetic states, revealing new therapeutic opportunities undetectable with standard approaches. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-42656-x |
| الإتاحة: | https://doi.org/10.1038/s41467-023-42656-xTest https://www.nature.com/articles/s41467-023-42656-x.pdfTest https://www.nature.com/articles/s41467-023-42656-xTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.F31F574B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-42656-x |
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