Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states

被引:87
|
作者
Song, Hanbing [1 ,2 ,3 ,4 ]
Weinstein, Hannah N. W. [1 ,2 ,3 ,4 ]
Allegakoen, Paul [1 ,2 ,3 ,4 ]
Wadsworth, Marc H. [5 ,6 ,7 ,8 ,9 ,10 ]
Xie, Jamie [1 ,2 ,3 ,4 ]
Yang, Heiko [2 ,11 ]
Castro, Ethan A. [1 ,2 ,3 ,4 ]
Lu, Kevin L. [12 ]
Stohr, Bradley A. [12 ]
Feng, Felix Y. [2 ,11 ,13 ]
Carroll, Peter R. [2 ,11 ]
Wang, Bruce [14 ]
Cooperberg, Matthew R. [2 ,11 ,15 ]
Shalek, Alex K. [5 ,6 ,7 ,8 ,9 ,10 ]
Huang, Franklin W. [1 ,2 ,3 ,4 ,15 ]
机构
[1] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Bakar Computat Hlth Sci Inst, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA
[5] MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[6] Harvard Univ, Cambridge, MA 02139 USA
[7] MIT, Inst Med Engn & Sci IMES, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[8] MIT, Dept Chem, Cambridge, MA 02139 USA
[9] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[10] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
[11] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA
[12] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA
[13] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA
[14] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA 94143 USA
[15] San Francisco VA Med Ctr, Dept Med, Div Hematol & Oncol, San Francisco, CA 94121 USA
基金
美国国家卫生研究院;
关键词
STEM-CELL; LUMINAL CELLS; IDENTIFICATION; EXPRESSION; PLASTICITY; MECHANISMS; PROSPECTS; EVOLUTION; BIOLOGY; ORIGIN;
D O I
10.1038/s41467-021-27322-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Prostate cancer is the second most common malignancy in men worldwide and consists of a mixture of tumor and non-tumor cell types. To characterize the prostate cancer tumor microenvironment, we perform single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. We uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer and identify a population of tumor-associated club cells that may be associated with prostate carcinogenesis. ERG-negative tumor cells, compared to ERG-positive cells, demonstrate shared heterogeneity with surrounding luminal epithelial cells and appear to give rise to common tumor microenvironment responses. Finally, we show that prostate epithelial organoids harbor tumor-associated epithelial cell states and are enriched with distinct cell types and states from their parent tissues. Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis. The changes that prostate cancer (PCa) induces in its microenvironment are not fully understood. Here the authors use single-cell RNA-seq and organoids to characterise how the microenvironment responds to PCa, and also identify tumour-associated epithelial cell states and club cells.
引用
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页数:20
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