Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression

被引：299

作者：

Chen, Sujun ^{[1
,2
,3
,4
]}

Zhu, Guanghui ^{[1
,2
,5
,6
]}

Yang, Yue ^{[1
]}

Wang, Fubo ^{[1
]}

Xiao, Yu-Tian ^{[1
]}

Zhang, Na ^{[7
]}

Bian, Xiaojie ^{[8
]}

Zhu, Yasheng ^{[1
]}

Yu, Yongwei ^{[1
]}

Liu, Fei ^{[9
]}

Dong, Keqin ^{[1
]}

Mariscal, Javier ^{[10
]}

Liu, Yin ^{[11
]}

Soares, Fraser ^{[2
]}

Loo Yau, Helen ^{[2
,3
]}

Zhang, Bo ^{[12
]}

Chen, Weidong ^{[12
]}

Wang, Chao ^{[12
]}

Chen, Dai ^{[12
]}

Guo, Qinghua ^{[12
]}

Yi, Zhengfang ^{[7
]}

Liu, Mingyao ^{[7
]}

Fraser, Michael ^{[2
]}

De Carvalho, Daniel D. ^{[2
,3
]}

Boutros, Paul C. ^{[3
,13
,14
,15
,16
,17
]}

Di Vizio, Dolores ^{[10
,18
,19
,20
]}

Jiang, Zhou ^{[21
]}

van der Kwast, Theodorus ^{[2
]}

Berlin, Alejandro ^{[2
,22
]}

Wu, Song ^{[5
,6
]}

Wang, Jianhua ^{[8
]}

He, Housheng Hansen ^{[2
,3
]}

Ren, Shancheng ^{[1
]}

机构：

[1] Shanghai Changhai Hosp, Dept Urol, Shanghai, Peoples R China

[2] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[3] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[4] Ontario Inst Canc Res, Toronto, ON, Canada

[5] Shenzhen Univ, Urol Inst, Affiliated Hosp 3, Shenzhen, Peoples R China

[6] Shenzhen Univ, Affiliated Luohu Hosp, Dept Urol Surg, Shenzhen, Peoples R China

[7] East China Normal Univ, Shanghai, Peoples R China

[8] Fudan Univ, Shanghai Canc Ctr, Inst Canc, Shanghai Urol Canc Inst, Shanghai, Peoples R China

[9] Chinese Acad Med Sci, Canc Hosp, Dept Urol, Shanghai, Peoples R China

[10] Cedars Sinai Med Ctr, Dept Surg, Div Canc Biol & Therapeut, Los Angeles, CA 90048 USA

[11] Tongji Univ, Sch Med, Dept Lab Med, Shanghai Pulm Hosp, Shanghai, Peoples R China

[12] Novel Bioinformat Co Ltd, Shanghai, Peoples R China

[13] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA

[14] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA

[15] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA

[16] Univ Calif Los Angeles, Inst Precis Hlth, Los Angeles, CA USA

[17] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada

[18] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Div Canc Biol & Therapeut, Los Angeles, CA 90048 USA

[19] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[20] Cedars Sinai Med Ctr, Dept Biomed Sci, Div Canc Biol & Therapeut, Los Angeles, CA 90048 USA

[21] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Pathol, Shanghai, Peoples R China

[22] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada

来源：

NATURE CELL BIOLOGY | 2021年 / 23卷 / 01期

关键词：

ENDOTHELIAL-CELLS; GENE-EXPRESSION; PROTEIN; DIAGNOSIS; MELANOMA; STATES;

D O I：

10.1038/s41556-020-00613-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Chen et al. perform single-cell analysis and identify transcriptomic remodelling in epithelial cells, macrophages, T cells, fibroblasts and endothelial cells, which together regulate prostate cancer progression. Prostate cancer shows remarkable clinical heterogeneity, which manifests in spatial and clonal genomic diversity. By contrast, the transcriptomic heterogeneity of prostate tumours is poorly understood. Here we have profiled the transcriptomes of 36,424 single cells from 13 prostate tumours and identified the epithelial cells underlying disease aggressiveness. The tumour microenvironment (TME) showed activation of multiple progression-associated transcriptomic programs. Notably, we observed promiscuous KLK3 expression and validated the ability of cancer cells in altering T-cell transcriptomes. Profiling of a primary tumour and two matched lymph nodes provided evidence that KLK3 ectopic expression is associated with micrometastases. Close cell-cell communication exists among cells. We identified an endothelial subset harbouring active communication (activated endothelial cells, aECs) with tumour cells. Together with sequencing of an additional 11 samples, we showed that aECs are enriched in castration-resistant prostate cancer and promote cancer cell invasion. Finally, we created a user-friendly web interface for users to explore the sequenced data.

引用

页码：87 / 98

页数：30

共 70 条

[31] Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles [J].

Minciacchi, Valentina R. ;

You, Sungyong ;

Spinelli, Cristiana ;

Morley, Samantha ;

Zandian, Mandana ;

Aspuria, Paul-Joseph ;

Cavallini, Lorenzo ;

Ciardiello, Chiara ;

Sobreiro, Mariana Reis ;

Morello, Matteo ;

Kharmate, Geetanjali ;

Jang, Su Chul ;

Kim, Dae-Kyum ;

Hosseini-Beheshti, Elham ;

Guns, Emma Tomlinson ;

Gleave, Martin ;

Gho, Yong Song ;

Mathivanan, Suresh ;

Yang, Wei ;

Freeman, Michael R. ;

Di Vizio, Dolores .

ONCOTARGET, 2015, 6 (13) :11327-11341

[32] Single-cell profiling of human gliomas reveals macrophage ontogeny as a basis for regional differences in macrophage activation in the tumor microenvironment [J].

Muller, Soren ;

Kohanbash, Gary ;

Liu, S. John ;

Alvarado, Beatriz ;

Carrera, Diego ;

Bhaduri, Aparna ;

Watchmaker, Payal B. ;

Yagnik, Garima ;

Di Lullo, Elizabeth ;

Malatesta, Martina ;

Amankulor, Nduka M. ;

Kriegstein, Arnold R. ;

Lim, Daniel A. ;

Aghi, Manish ;

Okada, Hideho ;

Diaz, Aaron .

GENOME BIOLOGY, 2017, 18

[33] Densely Interconnected Transcriptional Circuits Control Cell States in Human Hematopoiesis [J].

Novershtern, Noa ;

Subramanian, Aravind ;

Lawton, Lee N. ;

Mak, Raymond H. ;

Haining, W. Nicholas ;

McConkey, Marie E. ;

Habib, Naomi ;

Yosef, Nir ;

Chang, Cindy Y. ;

Shay, Tal ;

Frampton, Garrett M. ;

Drake, Adam C. B. ;

Leskov, Ilya ;

Nilsson, Bjorn ;

Preffer, Fred ;

Dombkowski, David ;

Evans, John W. ;

Liefeld, Ted ;

Smutko, John S. ;

Chen, Jianzhu ;

Friedman, Nir ;

Young, Richard A. ;

Golub, Todd R. ;

Regev, Aviv ;

Ebert, Benjamin L. .

CELL, 2011, 144 (02) :296-309

[34] Silencing of S100A4, a metastasis-associated protein, in endothelial cells inhibits tumor angiogenesis and growth [J].

Ochiya, Takahiro ;

Takenaga, Keizo ;

Endo, Hideya .

ANGIOGENESIS, 2014, 17 (01) :17-26

[35] BPG: Seamless, automated and interactive visualization of scientific data [J].

P'ng, Christine ;

Green, Jeffrey ;

Chong, Lauren C. ;

Waggott, Daryl ;

Prokopec, Stephenie D. ;

Shamsi, Mehrdad ;

Nguyen, Francis ;

Mak, Denise Y. F. ;

Lam, Felix ;

Albuquerque, Marco A. ;

Wu, Ying ;

Jung, Esther H. ;

Starmans, Maud H. W. ;

Chan-Seng-Yue, Michelle A. ;

Yao, Cindy Q. ;

Liang, Bianca ;

Lalonde, Emilie ;

Haider, Syed ;

Simone, Nicole A. ;

Sendorek, Dorota ;

Chu, Kenneth C. ;

Moon, Nathalie C. ;

Fox, Natalie S. ;

Grzadkowski, Michal R. ;

Harding, Nicholas J. ;

Fung, Clement ;

Murdoch, Amanda R. ;

Houlahan, Kathleen E. ;

Wang, Jianxin ;

Garcia, David R. ;

de Borja, Richard ;

Sun, Ren X. ;

Lin, Xihui ;

Chen, Gregory M. ;

Lu, Aileen ;

Shiah, Yu-Jia ;

Zia, Amin ;

Kearns, Ryan ;

Boutros, Paul C. .

BMC BIOINFORMATICS, 2019, 20 (1)

[36] p63 protein expression is rare in prostate adenocarcinoma: Implications for cancer diagnosis and carcinogenesis [J].

Parsons, JK ;

Gage, WR ;

Nelson, WG ;

De Marzo, AM .

UROLOGY, 2001, 58 (04) :619-624

[37] Differential expression of apoptotic genes PDIA3 and MAP3K5 distinguishes between low- and high-risk prostate cancer [J].

Pressinotti, Nicole Chui ;

Klocker, Helmut ;

Schaefer, Georg ;

Luu, Van-Duc ;

Ruschhaupt, Markus ;

Kuner, Ruprecht ;

Steiner, Eberhard ;

Poustka, Annemarie ;

Bartsch, Georg ;

Sueltmann, Holger .

MOLECULAR CANCER, 2009, 8

[38] Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer [J].

Puram, Sidharth V. ;

Tirosh, Itay ;

Parikh, Anuraag S. ;

Patel, Anoop P. ;

Yizhak, Keren ;

Gillespie, Shawn ;

Rodman, Christopher ;

Luo, Christina L. ;

Mroz, Edmund A. ;

Emerick, Kevin S. ;

Deschler, Daniel G. ;

Varvares, Mark A. ;

Mylvaganam, Ravi ;

Rozenblatt-Rosen, Orit ;

Rocco, James W. ;

Faquin, William C. ;

Lin, Derrick T. ;

Regev, Aviv ;

Bernstein, Bradley E. .

CELL, 2017, 171 (07) :1611-+

[39] The tumour hypoxia marker pimonidazole reflects a transcriptional programme associated with aggressive prostate cancer [J].

Ragnum, H. B. ;

Vlatkovic, L. ;

Lie, A. K. ;

Axcrona, K. ;

Julin, C. H. ;

Frikstad, K. M. ;

Hole, K. H. ;

Seierstad, T. ;

Lyng, H. .

BRITISH JOURNAL OF CANCER, 2015, 112 (02) :382-390

[40] Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study [J].

Ross-Adams, H. ;

Lamb, A. D. ;

Dunning, M. J. ;

Halim, S. ;

Lindberg, J. ;

Massie, C. M. ;

Egevad, L. A. ;

Russell, R. ;

Ramos-Montoya, A. ;

Vowler, S. L. ;

Sharma, N. L. ;

Kay, J. ;

Whitaker, H. ;

Clark, J. ;

Hurst, R. ;

Gnanapragasam, V. J. ;

Shah, N. C. ;

Warren, A. Y. ;

Cooper, C. S. ;

Lynch, A. G. ;

Stark, R. ;

Mills, I. G. ;

Groenberg, H. ;

Neal, D. E. .

EBIOMEDICINE, 2015, 2 (09) :1133-1144

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