Single-cell sequencing of tumor-associated macrophages in a Drosophila model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1014485 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25988000.fastq.gz | Fastqsanger.gz | |||
| SRR25988100_1.fastq.gz | Fastqsanger.gz | |||
| SRR25988100_2.fastq.gz | Fastqsanger.gz | |||
| SRR25988200.fastq.gz | Fastqsanger.gz | |||
| SRR25988300.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 542 |
Similar Datasets
Project description:Tumor-associated macrophages may act to either limit or promote tumor growth, yet the molecular basis for either path is poorly characterized. Using a Drosophila model for dysplastic growth during tumor early progression in combination with single-cell RNA sequencing of macrophage-like hemocytes, we identified 5 cell clusters. We included a second tumor model in our analysis where we inhibited the activation of effector caspases, partially mimicking apoptosis-resistant tumor cells. Circulating hemocytes from both tumor models differ qualitatively from control wild-type cells – they display an enrichment for genes involved in cell division, which was confirmed using proliferation assays. Split analysis of the tumor models further reveals that proliferation is strongest in the caspase-deficient setting. Similarly, depending on the tumor model, hemocytes that attach to tumors activate different sets of immune effectors – antimicrobial peptides dominate the response against the tumor alone, while caspase inhibition induces a shift toward members of proteolytic cascades. Finally, we find evidence for transcript transfer between hemocytes and possibly other tissues.
2023-09-08 | GSE242774 | GEO
Project description:The tumor microenvironment is highly complex and consists af many non-tumor cells and factors. To simplify the complexity, we developed a simple in vitro system where tumor (neuroblastoma) 'spheres' ~1-2 mm in diameter were generated on concave surfaces of noble agar. After sphere development, bone marrow-derived macrophages were added to the well. Many macrophages crawled into the spheres (as shown by live cell microscopy). After 24-28 h, the macrophages were isolated from inside or outside the tumor spheres using tissue digestion and anti-CD11b MACs beads. The macrophages from inside or outside the spheres were then subject to microarray analysis.
2016-05-02 | GSE68817 | GEO
Project description:IntroductionTumor-associated macrophages may act to either limit or promote tumor growth, yet the molecular basis for either path is poorly characterized.MethodsWe use a larval Drosophila model that expresses a dominant-active version of the Ras-oncogene (RasV12) to study dysplastic growth during early tumor progression. We performed single-cell RNA-sequencing of macrophage-like hemocytes to characterize these cells in tumor- compared to wild-type larvae. Hemocytes included manually extracted tumor-associated- and circulating cells.Results and discussionWe identified five distinct hemocyte clusters. In addition to RasV12 larvae, we included a tumor model where the activation of effector caspases was inhibited, mimicking an apoptosis-resistant setting. Circulating hemocytes from both tumor models differ qualitatively from control wild-type cells-they display an enrichment for genes involved in cell division, which was confirmed using proliferation assays. Split analysis of the tumor models further reveals that proliferation is strongest in the caspase-deficient setting. Similarly, depending on the tumor model, hemocytes that attach to tumors activate different sets of immune effectors-antimicrobial peptides dominate the response against the tumor alone, while caspase inhibition induces a shift toward members of proteolytic cascades. Finally, we provide evidence for transcript transfer between hemocytes and possibly other tissues. Taken together, our data support the usefulness of Drosophila to study the response against tumors at the organismic level.
| S-EPMC10546068 | biostudies-literature
Project description:Using a Drosophila model for dysplastic growth during tumor early progression in combination with single-cell RNA sequencing of macrophage-like hemocytes, we identified 5 cell clusters. We included a second tumor model in our analysis where we inhibited the activation of effector caspases, partially mimicking apoptosis-resistant tumor cells. Circulating hemocytes from both tumor models differ qualitatively from control wild-type cells – they display an enrichment for genes involved in cell division, which was confirmed using proliferation assays. Split analysis of the tumor models further reveals that proliferation is strongest in the caspase-deficient setting. Similarly, depending on the tumor model, hemocytes that attach to tumors activate different sets of immune effectors – antimicrobial peptides dominate the response against the tumor alone, while caspase inhibition induces a shift toward members of proteolytic cascades. Finally, we find evidence for transcript transfer between hemocytes and possibly other tissues.
| PRJEB65439 | ENA
Project description:Xenoline-polarized macrophages as a physiologically relevant in vitro model of tumor-associated macrophages in glioblastoma
| PRJNA1259443 | ENA
Project description:Tumor-associated macrophages (TAMs) are the most abundant non-cancerous cell type in glioblastoma (GBM) and heavily influence GBM biology, contributing to tumor progression, therapeutic resistance, immune evasion, and neovascularization. Current in vitro models that utilize IL-4/IL-13 stimulation fail to capture the transcriptional and functional heterogeneity of TAMs observed in vivo. In this study, we utilize a serum-free indirect co-culture model with patient-derived xenolines to polarize primary human macrophages and characterize their molecular and functional phenotypes. We demonstrate that xenoline-polarized macrophages diverge from classical M1/M2 states and instead adopt transcriptional signatures reflective of TAM subsets identified from patients. Notably, macrophages polarized with the radiation-therapy selected xenoline, JX14P-RT, exhibited gene expression patterns enriched for interferon response and hypoxia, mirroring recurrent GBM samples. In contrast, JX14P TAMs showed enrichment in phagocytic gene sets. Functional validation of these phenotypes revealed discrepancies between the transcriptionally predicted and observed phenotypes, emphasizing the importance of integrating phenotypic validation in sequencing studies. Altogether, our findings establish xenoline-polarized macrophages as a more physiologically relevant alternative to traditional models, offering a useful model for studying tumor-immune interaction in vitro.
2025-07-02 | GSE296472 | GEO
Project description:Murine macrophages: Peritoneal exudate macrophages (PECs) vs tumor-associated macrophages (TAMs)
| PRJNA704618 | ENA
Project description:Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an “alternatively activated” phenotype. TAM differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy. MMTV-PyMT mice (Jackson Laboratory) were backcrossed to the C57BL/6 background for 10 generations. Rbpjfl/fl mice were provided by Tasuku Honjo and crossed to CD11ccre mice provided by Boris Reizis. Littermate controls were used in all experiments when possible. All mice were maintained in a specific pathogen-free facility and animal experimentation was conducted in accordance with institutional guidelines. In the MMTV-PyMT spontaneous mammary tumor model, we found the key Notch transcriptional regulator, RBPJ, to be required for TAM terminal differentiation from inflammatory monocytes. The bulk myeloid cell population that remains in CD11cCreRbpj fl/fl mice (the cells in "Rbpj KO" samples), represents monocytes that have begun their differentiation into macrophages, but are unable to terminally differentiate due to the lack of Rbpj.
2014-04-18 | E-GEOD-56755 | biostudies-arrayexpress
Project description:Colorectal cancer is a major cause of mortality worldwide. Most patients develop colorectal liver metastases (CLM), and for such patients hepatectomy combined with chemotherapy may be curative. Nevertheless, in the era of precision medicine there is a critical need of prognostic markers to cope with the heterogeneity of CLM patients. Tumor-associated macrophages (TAMs) pave the way to tissue invasion and intravasation providing a nurturing microenvironment formetastases. The quantification of immune landscape of tumors has provided novel prognostic indicators of cancer progression, and the quantification of TAMs might explain the heterogeneity of CLM patients. Here, we will investigate the development of a new diagnostic tool based on TAMs with the aim to define the causative role of TAMs in CLM patients. This will open new clinical scenarios both for the diagnosis, therapy and prognosis, leading to the refinement of the therapeutic output in a personalized medicine perspective.
| 2300850 | ecrin-mdr-crc
Project description:Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAM) are often associated with poor prognosis in cancer. In order to better understand the influence of tumor cell apoptosis and in particular its effect on TAM, we investigated global gene expression signatures of undisturbed TAM engaged in engulfment of apoptotic tumor cells. We studied a xenograft model of an aggressive ‘starry-sky’ non-Hodgkin’s lymphoma, Burkitt’s lymphoma (BL), in which apoptotic tumor cells are common and frequently observed in association with the starry-sky TAM (SS-TAM, so called because they appear histologically as ‘stars’ in a ‘sky’ of tumor cells) that accumulate in these tumors. We used a BL cell line (BL2) whose cells phenotypically resemble the tumor biopsy cells from which the line was derived including the capacity to undergo apoptosis constitutively. BL xenografts in SCID mice closely recapitulated the starry-sky histological picture of the human lymphoma. Due to the high sensitivity of macrophages to their environments, we adopted laser-capture microdissection of individual SS-TAM in BL xenografts in order to obtain unbiased in situ transcriptional profiles of these cells, which we compared specifically with those of similarly-captured macrophages, the tingible-body macrophages from normal germinal centers (GCM). The rationale for this comparison was based upon BL being a germinal center malignancy and tingible-body macrophages being regarded as normal equivalents of SS-TAM. Gene expression profiles of SS-TAM from BL2 xenograft tumors were compared to splenic GCM profiles. Three mice from each group were analysed. RNA was isolated from 1000 captured macrophages from each mouse and global gene expression signatures were obtained using Affymetrix Mouse Gene 1.0 GeneChip arrays.
2014-12-20 | E-GEOD-64366 | biostudies-arrayexpress