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

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

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
Article number	5307
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-25624-1
Publication status	Published - 6 Sept 2021
Externally published	Yes

Keywords

Antineoplastic Agents/therapeutic use
Benzamides/therapeutic use
Cell Line, Tumor
Chromatin/chemistry
DNA, Neoplasm/genetics
Drug Resistance, Neoplasm/genetics
Exome Sequencing
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Neoplasm Proteins/genetics
Nitriles/therapeutic use
Phenylthiohydantoin/therapeutic use
Prostate/metabolism
Prostatic Neoplasms/drug therapy
Sequence Analysis, RNA/methods
Single-Cell Analysis/methods
Survival Analysis
Transcriptome

Access to Document

10.1038/s41467-021-25624-1Licence: CC BY

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

@article{237b78a0a6174145a34ae91999281f15,

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.",

keywords = "Antineoplastic Agents/therapeutic use, Benzamides/therapeutic use, Cell Line, Tumor, Chromatin/chemistry, DNA, Neoplasm/genetics, Drug Resistance, Neoplasm/genetics, Exome Sequencing, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Proteins/genetics, Nitriles/therapeutic use, Phenylthiohydantoin/therapeutic use, Prostate/metabolism, Prostatic Neoplasms/drug therapy, Sequence Analysis, RNA/methods, Single-Cell Analysis/methods, Survival Analysis, Transcriptome",

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 = sep,

day = "6",

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

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "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

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 - 2021/9/6

Y1 - 2021/9/6

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.

KW - Antineoplastic Agents/therapeutic use

KW - Benzamides/therapeutic use

KW - Cell Line, Tumor

KW - Chromatin/chemistry

KW - DNA, Neoplasm/genetics

KW - Drug Resistance, Neoplasm/genetics

KW - Exome Sequencing

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Male

KW - Neoplasm Proteins/genetics

KW - Nitriles/therapeutic use

KW - Phenylthiohydantoin/therapeutic use

KW - Prostate/metabolism

KW - Prostatic Neoplasms/drug therapy

KW - Sequence Analysis, RNA/methods

KW - Single-Cell Analysis/methods

KW - Survival Analysis

KW - Transcriptome

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

U2 - 10.1038/s41467-021-25624-1

DO - 10.1038/s41467-021-25624-1

M3 - Article

C2 - 34489465

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

Keywords

Access to Document

Other files and links

Fingerprint

Cite this