@article{01b3b34d471f4104897be776d14b9d79,
title = "Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse",
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.",
author = "S. Taavitsainen and N. Engedal and S. Cao and F. Handle and A. Erickson and S. Prekovic and D. Wetterskog and T. Tolonen and Vuorinen, {E. M.} and A. Kiviaho and R. N{\"a}tkin and T. H{\"a}kkinen and W. Devlies and S. Henttinen and R. Kaarij{\"a}rvi and M. Lahnalampi and H. Kaljunen and K. Nowakowska and H. Syv{\"a}l{\"a} and M. Bl{\"a}uer and P. Cremaschi and F. Claessens and T. Visakorpi and Tammela, {T. L.J.} and T. Murtola and Granberg, {K. J.} and Lamb, {A. D.} and K. Ketola and Mills, {I. G.} and G. Attard and W. Wang and M. Nykter and A. Urbanucci",
note = "Funding Information: We thank the Genomics Core Facility at Institute for Cancer Research (OUH; Oslo University Hospital, Oslo, Norway) for the support during preparation of the scATAC-and RNA-seq, the Tampere University histology core facility and Sari Toivola for skillful assistance during Visium experiments, and the UEF Bioinformatics Center, University of Eastern Finland, Finland. The study was financially supported by the Finnish Cultural Foundation (ST), Academy of Finland (#312043 (MN), #310829 (MN), #324009 (KK), #328928 (KK), #333545 (KG, EMV, and SH), #3121330724 (TM)), Finnish Cancer Society #3122800563 (TM) Cancer Foundation Finland (MN, KK, and KG), Sigrid Jus{\'e}lius Foundation (MN, KK, and KG), Emil Aaltonen Foundation (KG), Finnish Cancer Institute (MN), Norwegian Cancer Society (#198016-2018)(AU, NE), Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital (MN, TLJT, TV, and TM), The Norman Jaffe Professorship in Pediatrics Endowment Fund (SC), MD Anderson Colorectal Cancer Moon Shot Program (SC), Oncode Institute (SP), Finnish Cultural Foundation North Savo Regional fund (KK, RK), University of Eastern Finland Doctoral Programme in Molecular Medicine (RK), K. Albin Johansson Foundation (KK), John Black Foundation (IM), Human Cell Atlas Seed Network-Retina (WW), Chan Zuckerberg Institute (WW), NIH R01CA183793 (WW, SC), NIH R01CA239342 (WW), NIH R01CA158113 (WW), P30CA016672 (WW), the Fonds Wetenschappelijk Onderzoek-Vlaanderen #GOA9816N (FC), KU Leuven #C14/ 19/100 (FC), Kom op tegen Kanker #KOTK (FC, WD), Cancer Research UK # A22744 (GA, DW, KN, and PC), and Cancer Research UK #C57899/A25812 (AE, ADL). The results published here are in part based on data generated by The Cancer Genome Atlas project established by the NCI and NHGRI. Funding Information: GA receives a reward from the Institute of Cancer Research for his role as an inventor of abiraterone. GA has received honoraria, consulting fees, or travel support from Janssen, Astellas, Pfizer, Novartis, Bayer, Amgen, AstraZeneca, Sanofi, and Sapience, grant support from Janssen and Astellas, and is a principal investigator for clinical trials sponsored by Janssen, Pfizer, and Astellas. TM receives consultant fees from Astellas, Janssen, and Bayer; lecture fees from Novartis, Janssen, and Sanofi. He is a stockholder of Arocell ab. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
doi = "10.1038/s41467-021-25624-1",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
number = "1",
}
