| Autor: |
Sallamari Henttinen, Andrew Erickson, Roosa Kaarijärvi, Heidi Kaljunen, Tapio Visakorpi, Merja Bläuer, Alfonso Urbanucci, Mari Lahnalampi, Elisa M. Vuorinen, Paolo Cremaschi, Gerhardt Attard, Stefan Prekovic, Wout Devlies, Teuvo L.J. Tammela, Tomi Häkkinen, Karolina Nowakowska, Alastair D. Lamb, Sinja Taavitsainen, Shaolong Cao, Florian Handle, Antti Kiviaho, Teemu Tolonen, Kirsi Ketola, Heimo Syvälä, Daniel Wetterskog, Wenyi Wang, Kirsi J. Granberg, Ian G. Mills, Nikolai Engedal, Reetta Nätkin, Matti Nykter, Frank Claessens, Teemu J. Murtola |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-384422/v1 |
| Popis: |
Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond to systemic therapy. We employed single-cell assays for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identified pre-existing and treatment-persistent cell subpopulations that possess transcriptional stem-like features and regenerative potential when subjected to treatment. We found distinct chromatin landscapes associated with enzalutamide treatment and resistance that were linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent stem-like cells were able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal hitherto unrecognized molecular predictors of treatment response. This suggests that the high analytical resolution of pre-clinical models enabled by single-cell methods may powerfully inform clinical decision-making. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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