Subclonal cooperation drives metastasis through modulating local and systemic immune microenvironments
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA430336 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6496550.fastq.gz | Fastqsanger.gz | |||
| SRR6496560.fastq.gz | Fastqsanger.gz | |||
| SRR6496570.fastq.gz | Fastqsanger.gz | |||
| SRR6496580.fastq.gz | Fastqsanger.gz | |||
| SRR6496590.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 121 |
Similar Datasets
Project description:Most human tumours are heterogeneous, composed of cellular clones with different properties present at variable frequencies. Highly heterogeneous tumours have poor clinical outcomes, yet the underlying mechanism remains poorly understood. Here, we show that minor subclones of breast cancer cells expressing IL11 and FIGF (VEGFD) cooperate to promote metastatic progression and generate polyclonal metastases composed of driver and neutral subclones. Expression profiling of the epithelial and stromal compartments of monoclonal and polyclonal primary and metastatic lesions revealed that this cooperation is indirect, mediated through the local and systemic microenvironments. We identified neutrophils as a leukocyte population stimulated by the IL11-expressing minor subclone and showed that the depletion of neutrophils prevents metastatic outgrowth. Single-cell RNA-seq of CD45+ cell populations from primary tumours, blood and lungs demonstrated that IL11 acts on bone-marrow-derived mesenchymal stromal cells, which induce pro-tumorigenic and pro-metastatic neutrophils. Our results indicate key roles for non-cell-autonomous drivers and minor subclones in metastasis.
| S-EPMC6609451 | biostudies-literature
Project description:Bulk RNA-Seq: Gene expression analysis of stromal and tumor fractions of primary and metastatic lesions of polyclonal and monoclonal origin. Primary tumor control samples consist of monoclonal Thy1.1 (no replicates), monoclonal parental (no replicates), monoclonal IL11 (duplicate), monoclonal FIGF (duplicate), and monoclonal CFP (duplicate). Primary polyclonal tumor samples consist of separated Thy 1.1 (duplicate), CFP (no replicates), IL11 (triplicate), and FIGF (triplicate). Metastatic tumor samples consist of monoclonal CFP (duplicate), monoclonal IL11 (quadruplicate), monoclonal FIGF (quadruplicate), monoclonal Thy1.1 (duplicate), and polyclonal samples (duplicate). Metastatic stromal fractions consist of monoclonal CFP (duplicate), monoclonal FIGF (quadruplicate), monoclonal IL11 (quadruplicate), monoclonal parental (duplicate), monoclonal Thy1.1 (duplicate), and polyclonal samples (triplicate). Primary stromal samples consist of monoclonal CFP (duplicate), monoclonal FIGF (duplicate), monoclonal IL11 (duplicate), monoclonal parental (no replicates), monoclonal Thy1.1 (duplicate), and polyclonal samples (triplicate). Further stromal controls consisted of a single fatpad sample and lung sample. Single cell RNA-Seq: Blood, tumors and lungs were isolated from test groups (DOX+ and DOX-) and tumor-naïve animals. Samples were pooled across 3 animals per group, and CD45+populations were FACS-sorted. Two thousand single cells were targeted for each sample.
2019-09-24 | GSE109281 | GEO
Project description:Fragment-sequencing unveils local tissue microenvironments at single cell resolution
| PRJNA892532 | ENA
Project description:The spatial organization of cells within tissues is tightly linked to their biological function. Yet, methods to probe the entire transcriptome of multiple native tissue microenvironments at single cell resolution are lacking. Here, we introduce fragment-sequencing, a method that enables the transcriptomic characterization of single cells within spatially distinct tissue niches. Fragment-sequencing of the mouse metastatic liver revealed previously uncharacterized zonated genes and ligand-receptor interactions enriched in the different hepatic microenvironments and the metastatic niche.
2022-10-27 | GSE216189 | GEO
Project description:Leaf-to-leaf, systemic immune signaling known as systemic acquired resistance (SAR) is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to SAR in Arabidopsis thaliana, systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid (SA). Instead, we documented a moderate local but not systemic induction of abscisic acid (ABA) after infection of leaves with Psj. In contrast to SA or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or ABA triggered systemic immunity to Xtc. RNA-seq analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest and quantitative RT-PCR associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors possibly facilitating transcriptional reprogramming to potentiate immunity.
2014-11-24 | E-MTAB-3063 | biostudies-arrayexpress
Project description:Barley Systemic Immunity: Dataset Local and Systemic
| PRJEB7729 | ENA
Project description:Intratumoral heterogeneity (ITH) arises from distinct subclonal expansion following genetic or epigenetic alterations, and profoundly influences how tumors response to their immune microenvironment. Tumor progression trees based on single-cell mutational profiles have made it possible to trace subclonal evolution; however, conventional tree-building methods can incorporate only a limited number of cells and mutations, restricting their application to larger single-cell data. To investigate the effect of ITH on the therapeutic response of melanoma, we have developed Trisicell (https://trisicell.rtfd.io), a computational toolkit for scalable inference of mutational ITH through assessment of single-cell genomic variant data. By applying Trisicell to genetically matched mouse melanoma datasets, we found that expressed mutations are sufficient to effectively drive subclonal evolution. On single-cell, full-length RNA sequencing data of mouse melanoma from preclinical immune checkpoint blockade (ICB) studies, the analysis showed that the subtree-seeding mutations in the trees identified distinct subclones associated with a specific developmental state and neural crest lineage markers. Using the tree to trace cell lineages, we found that neoantigens depleted by ICB were predominantly expressed in minor subclones, suggesting that post-treatment recurrence is driven by immunoediting. Moreover, these neoantigens were enriched with those derived from frameshift mutations and mutated nuclear genes. Importantly, recurrently mutated genes in ICB-responding human melanoma exhibited the same features. We next used Trisicell to analyze single-cell, full-length RNA data of brain metastases (BM) from melanoma patients treated with ICB, and discovered that relapsing BM from ICB-responding patients exhibited subclones that also expressed a higher fraction of frameshift mutations and were associated with elevated levels of infiltrated T cells. Notably, they also exhibited more mutated HLA genes and expressed high level of the novel immune checkpoint HLA-G, a putative local immunosuppressive mechanism. In summary, applying Trisicell to single-cell transcriptomic analyses allowed us to identify novel features of ICB-responding melanoma neoantigens and distinct mechanisms for adapting to immunotherapy at different sites. These results have important implications for both melanoma evolution and target identification for immunotherapies, including ICB and cancer vaccines. This is the first study to trace subclonal evolution of neoantigens at single-cell resolution, demonstrating that Trisicell and our datasets represent important resources for the field.
2024-10-25 | GSE215960 | GEO
Project description:Itaconate-producing neutrophils regulate local and systemic inflammation following trauma
2023-11-08 | GSE221134 | GEO
Project description:In this study we activated subclonal differentiation in pancreatic adenocarcinoma cells to study the role of differentiated cells on tumor growth. Mesenchymal pancreatic adenocarcinoma (MiaPaCa) cells differentiated into adipose and endothelial cells to assess the tumor initiation potential of the differentiated cells and molecular changes associated with cell differentiation. Epithelial (TC-2742-2) cells expressed with Ebf2 were analyzed for its tumorigenic potential and molecular changes associated with Ebf2 expression.
2016-05-01 | GSE78014 | GEO
Project description:We perform bulk RNA sequencing, tumor/normal DNA sequencing, and spatial transcriptomics on an initial discovery cohort of eleven glioma samples (comprising oligodendrogliomas, astrocytomas, one diffuse midline glioma, and glioblastomas) to identify both commonalities and distinct characteristics within the tumor microenvironment. Six additional high-grade IDH wild-type, EGFR positive glioblastomas are analyzed to validate subclonal somatic aneuploidy and copy number alterations associated with extrachromosomal DNA double-minutes. As part of the standard spatial transcriptomic analysis, we develop an integrated analysis framework combining germline/tumor exomes, bulk RNA-seq, and spatial transcriptomics to identify loss of heterozygosity by a hidden Markov model for segmenting consecutively expressed SNPs. In the discovery cohort, we identify focally amplified ecDNA in four of the eleven cases, with subclonal tumor heterogeneity present in two EGFR-amplified grade IV glioblastomas. In a TP53-mutated glioblastoma, we detect a subclone with EGFR amplification on ecDNA coupled to chromosome 17 LOH. To evaluate the impact of spatial subclonal chromosomal alterations on the p53/EGFR axis, we examine six additional EGFR positive gliomas, identifying MDM2/MDM4 ecDNA subclones in two samples. The spatial DNA heterogeneity of EGFR and p53 inactivation underscores the role of ecDNA in enabling rapid oncogene amplification and enhancing tumor adaptability under selective pressure.
2025-01-02 | GSE242352 | GEO