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

2020 ◽  
Author(s):  
Hanbing Song ◽  
Hannah N.W. Weinstein ◽  
Paul Allegakoen ◽  
Marc H. Wadsworth ◽  
Jamie Xie ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Prostate Biopsies ◽  
Prostate Epithelial Cells ◽  
Cancer Tumor

AbstractProstate 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 performed single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. We identify a population of tumor-associated club cells that may act as progenitor cells and uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer. ERG- tumor cells, compared to ERG+ 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 recapitulate 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.

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

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Hanbing Song ◽  
Hannah N. W. Weinstein ◽  
Paul Allegakoen ◽  
Marc H. Wadsworth ◽  
Jamie Xie ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Prostate Biopsies ◽  
Prostate Carcinogenesis ◽  
Cancer Tumor

AbstractProstate 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.

Single-cell analysis of cellular state heterogeneity in human localized prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 254-254
Author(s):  
Hanbing Song ◽  
Hannah N.W. Weinstein ◽  
Paul Allegakoen ◽  
Marc Wadsworth ◽  
Jamie Xie ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Cells ◽  
Single Cell ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cellular Heterogeneity ◽  
Localized Prostate Cancer ◽  
State Transitions ◽  
Prostate Epithelial Cells

254 Background: Prostate cancer is the second most common malignancy in men worldwide. The development of cancer from prostate tissue involves complex interactions of tumor cells with surrounding epithelial and stromal cells and can occur multifocally, suggesting that prostate epithelial cells may undergo cellular state transitions towards carcinogenesis. Previous studies on localized prostate cancer molecular changes have focused on unsorted bulk tissue samples, leaving a gap in our understanding of the cellular heterogeneity in the tumor microenvironment. Single-cell analyses of tumor specimens have the potential to reveal, at unprecedented resolution, cellular composition, as well as instructive intercellular interactions. Methods: To characterize the localized prostate cancer tumor microenvironment, we performed single-cell RNA-sequencing (scRNA-seq) on prostate biopsies, radical prostatectomy specimens, and matched patient-derived organoids from localized prostate cancer patients. Results: Within prostate epithelial cells, we identified a population of club cells that may act as progenitor cells. Furthermore, we uncovered luminal-like epithelial cellular states augmented in androgen signaling across basal and club cell populations. By classifying tumor cells based on ERG expression status, we found that ERG- tumor cells, in contrast to ERG+ cells, share transcriptomic heterogeneity with surrounding luminal epithelial cells and are associated with common stromal and immune microenvironment responses. These results suggest that specific immune niches may arise based on TMPRSS2-ERG fusion status. Finally, we generated prostate epithelial organoids derived from matched localized prostate cancer patients and characterized their transcriptomic profiles by scRNA-seq. These patient-derived organoids recapitulated tumor-associated epithelial cell states but also harbored distinct cell types and states from their parent tissues. Conclusions: Our data from localized prostate cancer specimens and organoids provide diagnostically relevant insights and will help advance our understanding of the cancer cellular states associated with prostate carcinogenesis.

scholarly journals Single-cell RNA-Aequencing Reveals Novel Myofibroblasts with Epithelial Cell-Like Features in the Mammary Gland of Dairy Cattle

2020 ◽  
Author(s):  
Fengfei Gu ◽  
Jiajin Wu ◽  
Senlin Zhu ◽  
Teresa G. Valencak ◽  
Jian-Xin Liu ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Dairy Cattle ◽  
Single Cell ◽  
Dairy Product ◽  
Cell Types ◽  
Marker Genes ◽  
New Findings ◽  
Luminal Cells

Abstract Background: Cow’s milk is a highly-nutritious dairy product that is widely consumed worldwide. It is secreted by the developed mammary gland (MG) of dairy cattle. However, a comprehensive understanding of cell-type diversity and cell function within bovine MG is lacking. In the current study, we used single-cell RNA sequencing to investigate the transcriptome of 24,472 high-quality MG cells isolated from newborn and adult cows. Results: Unbiased clustering analysis revealed the existence of 24 cell types, which could be divided into four categories: 9 immune, 3 epithelial, 9 fibroblast, and 3 endothelial cell types. Other cell subtypes were further identified based on re-clustering and pseudotemporal reconstruction of epithelial cells that included 3 mature luminal epithelial, 1 intermediate, and 2 progenitor cell subtypes. The individual top marker genes of these 3 mature luminal epithelial cell subtypes (L0, L1, and L5) were APOA1, STC2, and PTX3, which were further validated using immunofluorescence. Based on functional analysis, the L0, L1, and L5 cell subtypes were all involved in the upregulation of lipid metabolism, protein and hormone metabolism, and the immune response, respectively. Furthermore, we discovered a novel myofibroblast that expresses COL1A1 and CSN3, has visible epithelial-like characteristics, and shows the potential to differentiate into luminal epithelial cells, especially immune-sensing luminal cells (L5). Conclusions: We constructed the first single-cell atlas of the dairy cow MG, and our new findings of epithelial-like myofibroblast cells and their differentiation trajectories into luminal cells may provide novel insights into the development and lactogenesis in dairy cattle MGs.

scholarly journals Prostate Epithelial Genes Define Docetaxel-Sensitive Prostate Cancer Molecular Subtype

2020 ◽  
Author(s):  
Hyunho Han ◽  
Kwibok Choi ◽  
Young Jun Moon ◽  
Ji Eun Heo ◽  
Won Sik Ham ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Single Cell ◽  
Molecular Subtype ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Prostate Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Subtype B ◽  
Prostate Epithelial Cells

ABSTRACTBACKGROUND & OBJECTIVESAnalysis of the transcriptomic landscape of prostate adenocarcinoma shows multidimensional gene expression variability. Understanding cancer transcriptome complexity can provide biological insight and therapeutic guidance. To avoid potential confounding factors, such as stromal contamination and stress-related material degradation, we utilized a set of genes expressed by prostate epithelial cells from single-cell transcriptome data of the human prostate gland.MATERIALS & METHODSAnalyzing publicly available bulk and single-cell RNA sequencing data, we defined 1,629 genes expressed by prostate epithelial cells. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival.RESULTSTCGA-PRAD tumors were separated into four subtypes: A (30.0%), B (26.0%), C (14.7%), D (4.2%), and mixed (25.0%). Subtype A was characterized by low frequency of ETS-family fusions and high expression of KLK3, which encodes prostate-specific antigen (PSA). Subtype B showed the highest expression of ACP3, encoding PAP (prostatic acid phosphatase). Subtypes C and D were commonly associated with advanced T/N stages, high Gleason grades, and p53 or PIK3CA mutations. In silico drug-sensitivity screening suggested that subtype B is likely sensitive to docetaxel and paclitaxel. Serum PSA/PAP ratio was predictive of a radiographic response to docetaxel in metastatic castration-resistant prostate cancer patients.CONCLUSIONWe propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents. Molecular subtypes and biomarkers must be validated in a prospective cohort study.

scholarly journals Single-cell RNA-seq analysis reveals lung epithelial cell-specific contributions of Tet1 to allergic inflammation

2021 ◽  
Author(s):  
Tao Zhu ◽  
Anthony P Brown ◽  
Lucy Cai ◽  
Gerald Quon ◽  
Hong Ji
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Single Cell ◽  
Lung Inflammation ◽  
Trajectory Analysis ◽  
Cell Types ◽  
Lung Epithelial Cells ◽  
Lung Epithelial Cell ◽  
Alveolar Type ◽  
Lung Epithelial

Background: Tet1 protects against house dust mite (HDM)-induced lung inflammation in mice and alters the lung methylome and transcriptome. We explored the role of Tet1 in individual lung epithelial cell types in HDM-induced inflammation. Methods: A model of HDM-induced lung inflammation was established in Tet1 knockout and littermate wildtype mice. EpCAM+ lung epithelial cells were isolated. Libraries were generated using the 10X Chromium workflow and sequenced. ScRNA-seq analysis was performed using Cell Ranger, scAlign, and Seurat. Cell types were labeled using known markers. Enriched pathways were identified using Ingenuity Pathway Analysis. Transcription factor (TF) activity was analyzed by DoRothEA. Single-cell trajectory analysis was performed with Monocle to explore Alveolar type 2 (AT2) cell differentiation. Results: AT2 cells were the most abundant among the eight EpCAM+ lung epithelial cell types. HDM challenge increased the percentage of alveolar progenitor cells (AP), broncho alveolar stem cells (BAS), and goblet cells, and decreased the percentage of AT2 and ciliated cells. Bulk and cell-type-specific analysis identified genes subject to Tet1 regulation and linked to augmented lung inflammation, including alarms, detoxification enzymes and oxidative stress response genes, and gene in tissue repair. The transcriptomic regulation was accompanied by alterations in TF activities. Trajectory analysis supports that HDM may enhance the differentiation of AP and BAS cells into AT2 cells, independent of Tet1. Conclusions: Collectively, lung epithelial cells had common and unique transcriptomic signatures of allergic lung inflammation. Tet1 deletion altered transcriptomic networks in various lung epithelial cells, with an overall effect of promoting allergen-induced lung inflammation.

scholarly journals Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq

2018 ◽  
Author(s):  
Jianhua Yin ◽  
Zhisheng Li ◽  
Chen Yan ◽  
Enhao Fang ◽  
Ting Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Cell Types ◽  
Rna Seq ◽  
Breast Cancer Patients ◽  
Numerous Cell ◽  
Cancer Tumor

AbstractThe tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer by single-cell RNA-seq. We profiled the breast cancer tumor microenvironment by analyzing the single-cell transcriptomes of 52,163 cells from the tumor tissues of 15 breast cancer patients. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level. This study explores the diversity of the cell types in the tumor microenvironment and provides information on the mechanisms of escape from clearance by immune cells in breast cancer.One Sentence SummaryLandscape of tumor cells and immune cells in breast cancer by single cell RNA-seq

scholarly journals Single-cell analysis of human adipose tissue identifies depot- and disease-specific cell types

2019 ◽  
Vol 2 (1) ◽  
pp. 97-109 ◽  
Author(s):  
Jinchu Vijay ◽  
Marie-Frédérique Gauthier ◽  
Rebecca L. Biswell ◽  
Daniel A. Louiselle ◽  
Jeffrey J. Johnston ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Human Adipose Tissue ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Analysis ◽  
Disease Specific

scholarly journals GPX1 Localizes to the Nucleus in Prostate Epithelium and its Levels are not Associated with Prostate Cancer Recurrence

Antioxidants ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 167 ◽  
Author(s):  
Dede Ekoue ◽  
Emmanuel Ansong ◽  
Lenny Hong ◽  
Larisa Nonn ◽  
Virgilia Macias ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Prostate Cancer Risk ◽  
Cancer Recurrence ◽  
Lipid Peroxides ◽  
Cancer Tissue ◽  
Nuclear Staining ◽  
Dietary Intakes ◽  
Prostate Epithelial Cells ◽  
Prostate Cancer Recurrence

Glutathione peroxidase 1 (GPX1) is an extensively studied selenium-dependent protein that reduces hydrogen and lipid peroxides to water. Because of its antioxidant function and its responsiveness to dietary intakes of selenium, an essential trace element whose levels are inversely associated with prostate cancer risk, GPX1 levels were assessed in a prostate cancer tissue microarray, comparing cases of recurrent prostate cancer following prostatectomy to non-recurrent controls. While GPX1 is generally considered as a protein that resides in both the cytoplasm and mitochondria, we detected strong nuclear staining by immunofluorescence using GPX1-specific antibodies. Nuclear localization of GPX1 was also observed in both primary prostate epithelial cells and the immortalized prostate-derived cell line RWPE-1, but not in LNCaP or PC3 prostate tumor-derived cell lines. Quantification of GPX1 levels in the entire cell, the cytoplasm, and the nucleus did not indicate any association of either its levels or subcellular distribution with prostate cancer recurrence. While GPX1 levels may not have an impact on survival among men with prostate cancer, the data indicates that this extensively characterized protein may have a novel function in the nucleus of prostate epithelial cells.

Sign in / Sign up

Export Citation Format

Share Document