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

Author

Listed:
  • S. Taavitsainen

    (Tampere University and Tays Cancer Center)

  • N. Engedal

    (Oslo University Hospital)

  • S. Cao

    (The University of Texas MD Anderson Cancer Center)

  • F. Handle

    (Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven
    Medical University of Innsbruck)

  • A. Erickson

    (University of Oxford)

  • S. Prekovic

    (Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute)

  • D. Wetterskog

    (University College London Cancer Institute)

  • T. Tolonen

    (Tampere University and Tays Cancer Center
    Tampere University Hospital)

  • E. M. Vuorinen

    (Tampere University and Tays Cancer Center)

  • A. Kiviaho

    (Tampere University and Tays Cancer Center)

  • R. Nätkin

    (Tampere University and Tays Cancer Center)

  • T. Häkkinen

    (Tampere University and Tays Cancer Center)

  • W. Devlies

    (Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven
    Department of Urology, UZ Leuven)

  • S. Henttinen

    (Tampere University and Tays Cancer Center)

  • R. Kaarijärvi

    (University of Eastern Finland)

  • M. Lahnalampi

    (University of Eastern Finland)

  • H. Kaljunen

    (University of Eastern Finland)

  • K. Nowakowska

    (University College London Cancer Institute)

  • H. Syvälä

    (Tampere University and Tays Cancer Center)

  • M. Bläuer

    (Tampere University and Tays Cancer Center)

  • P. Cremaschi

    (University College London Cancer Institute)

  • F. Claessens

    (Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven)

  • T. Visakorpi

    (Tampere University and Tays Cancer Center
    Tampere University Hospital)

  • T. L. J. Tammela

    (Tampere University and Tays Cancer Center)

  • T. Murtola

    (Tampere University and Tays Cancer Center)

  • K. J. Granberg

    (Tampere University and Tays Cancer Center)

  • A. D. Lamb

    (University of Oxford
    Department of Urology, Churchill Hospital Cancer Centre)

  • K. Ketola

    (University of Eastern Finland)

  • I. G. Mills

    (University of Oxford
    Queen’s University of Belfast
    University of Bergen)

  • G. Attard

    (University College London Cancer Institute)

  • W. Wang

    (The University of Texas MD Anderson Cancer Center)

  • M. Nykter

    (Tampere University and Tays Cancer Center)

  • A. Urbanucci

    (Oslo University Hospital)

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.

Suggested Citation

  • 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. Kaar, 2021. "Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25624-1
    DOI: 10.1038/s41467-021-25624-1
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    Cited by:

    1. Sukanya Panja & Mihai Ioan Truica & Christina Y. Yu & Vamshi Saggurthi & Michael W. Craige & Katie Whitehead & Mayra V. Tuiche & Aymen Al-Saadi & Riddhi Vyas & Shridar Ganesan & Suril Gohel & Frederic, 2024. "Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    2. Goutam Chakraborty & Kasmira Gupta & Natasha Kyprianou, 2023. "Epigenetic mechanisms underlying subtype heterogeneity and tumor recurrence in prostate cancer," Nature Communications, Nature, vol. 14(1), pages 1-4, December.
    3. Jeroen Kneppers & Tesa M. Severson & Joseph C. Siefert & Pieter Schol & Stacey E. P. Joosten & Ivan Pak Lok Yu & Chia-Chi Flora Huang & Tunç Morova & Umut Berkay Altıntaş & Claudia Giambartolomei & Ji, 2022. "Extensive androgen receptor enhancer heterogeneity in primary prostate cancers underlies transcriptional diversity and metastatic potential," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Thomas C. Westbrook & Xiangnan Guan & Eva Rodansky & Diana Flores & Chia Jen Liu & Aaron M. Udager & Radhika A. Patel & Michael C. Haffner & Ya-Mei Hu & Duanchen Sun & Tomasz M. Beer & Adam Foye & Rah, 2022. "Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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