Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse
Year: 2021
Type: article
Abstract: Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond to systemic therapy. Here, we employ 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 identify pre-existing and treatment-persistent cell subpopulations that possess regenerative potential when subjected to treatment. We find distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent cells are 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 as yet unrecognized molecular predictors of treatment response. This suggests that the application of single-cell methods with high analytical resolution in pre-clinical models may powerfully inform clinical decision-making.
Source: Nature Communications
Authors: S. Taavitsainen, N. Engedal, S. Cao, F. Handle, A. Erickson, S. Prekovic, D. Wetterskog, T. Tolonen, E. M. Vuorinen, A. Kiviaho, R. Nätkin, T. Häkkinen, W. Devlies, S. Henttinen, R. Kaarijärvi, M. Lahnalampi, H. Kaljunen, K. Nowakowska, H. Syvälä, M. Bläuer, P. Cremaschi, F. Claessens, T. Visakorpi, T. L. J. Tammela, T. Murtola, K. J. Granberg, A. D. Lamb, K. Ketola, I. G. Mills, G. Attard, W. Wang, M. Nykter, A. Urbanucci
Institutions: Tampere University, University of Tampere, Oslo University Hospital, The University of Texas MD Anderson Cancer Center, Innsbruck Medical University, Universität Innsbruck, KU Leuven, University of Oxford, The Netherlands Cancer Institute, Oncode Institute, University College London, Tampere University Hospital, Fimlab (Finland), Universitair Ziekenhuis Leuven, University of Eastern Finland, Churchill Hospital, Queen's University Belfast, University of Bergen
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,885
Funders: Itä-Suomen Yliopisto, Kreftforeningen, Finnish Cancer Institute, Cancer Research UK, National Institute for Health and Care Research, Academy of Medical Sciences, Academy of Finland, Suomen Kulttuurirahasto, Fonds Wetenschappelijk Onderzoek, KU Leuven, Emil Aaltosen Säätiö, Sigrid Juséliuksen Säätiö, K. Albin Johanssons Stiftelse, Tays, Syöpäsäätiö, Kom op tegen Kanker, Vlaamse regering, Oncode Institute, National Institutes of Health, University of Texas MD Anderson Cancer Center, Pohjois-Savon Rahasto, National Human Genome Research Institute, National Cancer Institute
Awards: G1116275933, Consistent variable selection in p>>n settings, G293715275, G3058303973, Statistical methods for genomic analysis of heterogeneous tumors, G4327696449, G4601364635, Classical and non-classical actions of androgens and their receptor, G5653589078, G7370299342, G8363072258, G8948234362, Cancer Center Support Grant, G938023480, Statistical methods and tools for cancer risk prediction in families with germline mutations in TP53, G981328206
OpenAlex ID: W3197037991