scholarly journals Single-Cell RNA Sequencing Identifies Extracellular Matrix Gene Expression by Pancreatic Circulating Tumor Cells

Cell Reports ◽  
2014 ◽  
Vol 8 (6) ◽  
pp. 1905-1918 ◽  
Author(s):  
David T. Ting ◽  
Ben S. Wittner ◽  
Matteo Ligorio ◽  
Nicole Vincent Jordan ◽  
Ajay M. Shah ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Single Cell ◽  
Tumor Cells ◽  
Rna Sequencing ◽  
Circulating Tumor Cells ◽  
Matrix Gene ◽  
Single Cell Rna Sequencing

scholarly journals Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations

Oncogene ◽  
2020 ◽  
Author(s):  
Di He ◽  
Di Wang ◽  
Ping Lu ◽  
Nan Yang ◽  
Zhigang Xue ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Single Cell ◽  
Tumor Cells ◽  
Rna Sequencing ◽  
Early Stage ◽  
Cell Types ◽  
Egfr Mutations ◽  
Advanced Tumor ◽  
Single Cell Rna Sequencing

Abstract Lung adenocarcinoma (LUAD) harboring EGFR mutations prevails in Asian population. However, the inter-patient and intra-tumor heterogeneity has not been addressed at single-cell resolution. Here we performed single-cell RNA sequencing (scRNA-seq) of total 125,674 cells from seven stage-I/II LUAD samples harboring EGFR mutations and five tumor-adjacent lung tissues. We identified diverse cell types within the tumor microenvironment (TME) in which myeloid cells and T cells were the most abundant stromal cell types in tumors and adjacent lung tissues. Within tumors, accompanied by an increase in CD1C+ dendritic cells, the tumor-associated macrophages (TAMs) showed pro-tumoral functions without signature gene expression of defined M1 or M2 polarization. Tumor-infiltrating T cells mainly displayed exhausted and regulatory T-cell features. The adenocarcinoma cells can be categorized into different subtypes based on their gene expression signatures in distinct pathways such as hypoxia, glycolysis, cell metabolism, translation initiation, cell cycle, and antigen presentation. By performing pseudotime trajectory, we found that ELF3 was among the most upregulated genes in more advanced tumor cells. In response to secretion of inflammatory cytokines (e.g., IL1B) from immune infiltrates, ELF3 in tumor cells was upregulated to trigger the activation of PI3K/Akt/NF-κB pathway and elevated expression of proliferation and anti-apoptosis genes such as BCL2L1 and CCND1. Taken together, our study revealed substantial heterogeneity within early-stage LUAD harboring EGFR mutations, implicating complex interactions among tumor cells, stromal cells and immune infiltrates in the TME.

Abstract IA09: Single cell RNA-sequencing of circulating tumor cells

2016 ◽  
Author(s):  
David T. Miyamoto ◽  
Yu Zheng ◽  
Ben S. Wittner ◽  
Richard J. Lee ◽  
Huili Zhu ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Cells ◽  
Rna Sequencing ◽  
Circulating Tumor Cells ◽  
Single Cell Rna Sequencing

scholarly journals Whole transcriptomics analyses of mimicking circulating tumor cells (CTCs) by single-cell RNA sequencing (scRNAseq)

2019 ◽  
Vol 30 ◽  
pp. v13 ◽  
Author(s):  
J. Garcia ◽  
F. Monjaret ◽  
F. Geiguer ◽  
J.-P. Aurel ◽  
A. Puisieux ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Cells ◽  
Rna Sequencing ◽  
Circulating Tumor Cells ◽  
Single Cell Rna Sequencing

scholarly journals Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yu-Heng Cheng ◽  
Yu-Chih Chen ◽  
Eric Lin ◽  
Riley Brien ◽  
Seungwon Jung ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Cells ◽  
Rna Sequencing ◽  
Circulating Tumor Cells ◽  
High Throughput ◽  
Single Cell Rna Sequencing

Dissecting the immune infiltrate induced by ADT and PD-1 blockade in men with metastatic hormone-sensitive prostate cancer using single-cell RNA-sequencing.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17548-e17548
Author(s):  
Jessica Hawley ◽  
Aleksandar Obradovic ◽  
Xinzheng Victor Guo ◽  
Matthew Chaimowitz ◽  
Clara A Easterlin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Single Cell ◽  
Tumor Cells ◽  
Rna Sequencing ◽  
Metastatic Tumor ◽  
Immune Infiltrate ◽  
Single Cell Rna Sequencing ◽  
Hormone Sensitive ◽  
Tumor Biopsies

e17548 Background: Overall survival of men with de novo metastatic, hormone-sensitive prostate cancer (mHSPC) is improved by treatment intensification with docetaxel and hormone therapy compared to androgen deprivation therapy (ADT) alone. However, castration-resistant prostate cancer (CRPC) invariably develops. We and others have shown that ADT induces a robust and complex immune infiltrate in localized prostate cancer, in both animal models and humans. We are conducting a clinical trial (NCT03951831) to test the hypothesis that the ADT-induced immune infiltrate can be further augmented with chemotherapy and an anti-PD-1 inhibitor in men with mHSPC. Here, we present single-cell RNA-sequencing analysis of paired metastatic tumor biopsies at baseline and on-treatment. Methods: In our phase 2, open-label, single-center trial, eligible patients with mHSPC are treated with phased administration of ADT, cemiplimab (anti-PD-1 inhibitor), and docetaxel. All patients undergo baseline metastatic tumor biopsies as well as on-treatment biopsies after either ADT alone or ADT in combination with cemiplimab. Biopsies are dissociated by gentleMACS protocol, and single cells are sequenced using the 10X Chromium platform. Cells are Quality-control filtered to those with over 1000 Unique Molecular Identifiers and less than 25% mitochondrial RNA, then clustered on global gene expression and on inferred protein activity by unsupervised Louvain algorithm with silhouette score selection of optimal clustering resolution. Cell types are assigned by the singleR algorithm and tumor cell identity is verified by inference of Copy Number Variations (InferCNV). Differential gene expression across sub-clusters is performed, and baselines will be compared to their paired on-treatment sample (N = 3). Results: Preliminary results showed a significant increase in the normalized fold-change of CD8+ T cells in on-treatment samples relative to baseline samples (P < 0.001). There was also a dramatic increase in other immune cell subtypes with treatment. In addition, we found a shift in transcriptional state of tumor cells and that tumor cells expressing KLK2/KLK3 significantly dissipate with treatment (normalized fold-change 0.56, P < 0.001). Conclusions: Taken together these show the feasibility of SS-RNA-seq on PC metastatic lesions and provide initial support for the hypothesis that ADT induces complex immunological changes in the tumor microenvironment (TME) in metastatic prostate tumors.

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