Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse

Nat Commun. 2021 Sep 6;12(1):5307. doi: 10.1038/s41467-021-25624-1.

S Taavitsainen ¹, N Engedal ², S Cao ³, F Handle ⁴ ⁵, A Erickson ⁶, S Prekovic ⁷, D Wetterskog ⁸, T Tolonen ¹ ⁹, E M Vuorinen ¹, A Kiviaho ¹, R Nätkin ¹, T Häkkinen ¹, W Devlies ⁴ ¹⁰, S Henttinen ¹, R Kaarijärvi ¹¹, M Lahnalampi ¹¹, H Kaljunen ¹¹, K Nowakowska ⁸, H Syvälä ¹, M Bläuer ¹, P Cremaschi ⁸, F Claessens ⁴, T Visakorpi ¹² ¹³, T L J Tammela ¹, T Murtola ¹, K J Granberg ¹, A D Lamb ⁶ ¹⁴, K Ketola ¹¹, I G Mills ⁶ ¹⁵ ¹⁶, G Attard ⁸, W Wang ³, M Nykter ¹⁷, A Urbanucci ¹⁸

Affiliations

1 Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland.
2 Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
3 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
4 Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
5 Department of Urology, Division of Experimental Urology, Medical University of Innsbruck, Innsbruck, Austria.
6 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
7 Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
8 University College London Cancer Institute, London, UK.
9 Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
10 Department of Urology, UZ Leuven, Leuven, Belgium.
11 Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
12 Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland.
13 Fimlab Laboratories, Ltd, Tampere University Hospital, Tampere, Finland.
14 Department of Urology, Churchill Hospital Cancer Centre, Oxford, UK.
15 Patrick G Johnston Centre for Cancer Research, Queen's University of Belfast, Belfast, UK.
16 Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway.
17 Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland. [email protected].
18 Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. [email protected].

PMID: 34489465 DOI: 10.1038/s41467-021-25624-1

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.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-70002

Enzalutamide

99.96%, Androgen Receptor Antagonist

Androgen Receptor; Autophagy

Cancer

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