Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states
Autor: | Song, Hanbing, Weinstein, Hannah N. W., Allegakoen, Paul, Wadsworth, Marc H., Xie, Jamie, Yang, Heiko, Castro, Ethan A., Lu, Kevin L., Stohr, Bradley A., Feng, Felix Y., Carroll, Peter R., Wang, Bruce, Cooperberg, Matthew R., Shalek, Alex K., Huang, Franklin W. |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Cancer microenvironment
Male Urologic Diseases Aging Carcinogenesis Tumour heterogeneity Science Primary Cell Culture General Physics and Astronomy Article General Biochemistry Genetics and Molecular Biology Genetic Heterogeneity Transcriptional Regulator ERG Clinical Research Cancer genomics Tumor Microenvironment Humans 2.1 Biological and endogenous factors Cell Lineage Aetiology Cancer models Cancer Prostatectomy Neoplastic Prostate cancer Multidisciplinary Gene Expression Profiling Prostate Cancer Prostate Prostatic Neoplasms Epithelial Cells Molecular Sequence Annotation General Chemistry Neoplasm Proteins Gene Expression Regulation Neoplastic Organoids Gene Ontology Gene Expression Regulation Single-Cell Analysis Signal Transduction |
Zdroj: | Nature Communications, Vol 13, Iss 1, Pp 1-20 (2022) Nature communications, vol 13, iss 1 Nature Communications |
ISSN: | 2041-1723 |
Popis: | 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. |
Databáze: | OpenAIRE |
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