Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states
Hanbing Song,
Hannah N. W. Weinstein,
Paul Allegakoen,
Marc H. Wadsworth,
Jamie Xie,
Heiko Yang,
Ethan A. Castro,
Kevin L. Lu,
Bradley A. Stohr,
Felix Y. Feng,
Peter R. Carroll,
Bruce Wang,
Matthew R. Cooperberg,
Alex K. Shalek and
Franklin W. Huang ()
Additional contact information
Hanbing Song: University of California, San Francisco
Hannah N. W. Weinstein: University of California, San Francisco
Paul Allegakoen: University of California, San Francisco
Marc H. Wadsworth: Massachusetts Institute of Technology and Harvard University
Jamie Xie: University of California, San Francisco
Heiko Yang: University of California, San Francisco
Ethan A. Castro: University of California, San Francisco
Kevin L. Lu: University of California, San Francisco
Bradley A. Stohr: University of California, San Francisco
Felix Y. Feng: University of California, San Francisco
Peter R. Carroll: University of California, San Francisco
Bruce Wang: University of California
Matthew R. Cooperberg: University of California, San Francisco
Alex K. Shalek: Massachusetts Institute of Technology and Harvard University
Franklin W. Huang: University of California, San Francisco
Nature Communications, 2022, vol. 13, issue 1, 1-20
Abstract:
Abstract 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.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27322-4
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DOI: 10.1038/s41467-021-27322-4
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