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

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

doi:10.1038/s41467-021-25624-1

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

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. BläuerP. 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

Bioinformatics & Computational Biology

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

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.

Original language	English (US)
Article number	5307
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-25624-1
State	Published - Dec 1 2021

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

MD Anderson CCSG core facilities

Bioinformatics Shared Resource

Access to Document

10.1038/s41467-021-25624-1

Cite this

Taavitsainen, S., Engedal, N., Cao, S., Handle, F., Erickson, A., Prekovic, S., Wetterskog, D., Tolonen, T., Vuorinen, E. M., Kiviaho, A., Nätkin, R., Häkkinen, T., Devlies, W., Henttinen, S., Kaarijärvi, R., Lahnalampi, M., Kaljunen, H., Nowakowska, K., Syvälä, H., ... Urbanucci, A. (2021). Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse. Nature communications, 12(1), Article 5307. https://doi.org/10.1038/s41467-021-25624-1

Taavitsainen, S, Engedal, N, Cao, S, Handle, F, Erickson, A, Prekovic, S, Wetterskog, D, Tolonen, T, Vuorinen, EM, Kiviaho, A, Nätkin, R, Häkkinen, T, Devlies, W, Henttinen, S, Kaarijärvi, R, Lahnalampi, M, Kaljunen, H, Nowakowska, K, Syvälä, H, Bläuer, M, Cremaschi, P, Claessens, F, Visakorpi, T, Tammela, TLJ, Murtola, T, Granberg, KJ, Lamb, AD, Ketola, K, Mills, IG, Attard, G, Wang, W, Nykter, M & Urbanucci, A 2021, 'Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse', Nature communications, vol. 12, no. 1, 5307. https://doi.org/10.1038/s41467-021-25624-1

@article{75705787385d4dbca781413b1e7d166f,

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 = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-021-25624-1",

language = "English (US)",

volume = "12",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse

AU - Taavitsainen, S.

AU - Engedal, N.

AU - Cao, S.

AU - Handle, F.

AU - Erickson, A.

AU - Prekovic, S.

AU - Wetterskog, D.

AU - Tolonen, T.

AU - Vuorinen, E. M.

AU - Kiviaho, A.

AU - Nätkin, R.

AU - Häkkinen, T.

AU - Devlies, W.

AU - Henttinen, S.

AU - Kaarijärvi, R.

AU - Lahnalampi, M.

AU - Kaljunen, H.

AU - Nowakowska, K.

AU - Syvälä, H.

AU - Bläuer, M.

AU - Cremaschi, P.

AU - Claessens, F.

AU - Visakorpi, T.

AU - Tammela, T. L.J.

AU - Murtola, T.

AU - Granberg, K. J.

AU - Lamb, A. D.

AU - Ketola, K.

AU - Mills, I. G.

AU - Attard, G.

AU - Wang, W.

AU - Nykter, M.

AU - Urbanucci, A.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85114649041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85114649041&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-25624-1

DO - 10.1038/s41467-021-25624-1

M3 - Article

C2 - 34489465

AN - SCOPUS:85114649041

SN - 2041-1723

VL - 12

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 5307

ER -

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

Other files and links

Fingerprint

Cite this