The transcriptional profile of neutrophils in different organs during pancreatic cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE150061 | GEO | 2020/05/08
REPOSITORIES: GEO
Similar Datasets
Project description:We report that tumor-infiltrating neutrophils are significantly different from their bone marrow and circulating neutrophils counterparts. We generated a heatmap clustering of the differentially expressed genes between the neutrophils from the three compartments, and identified four distinct gene clusters. Notably, genes in cluster 1 were down-regulated in tumor neutrophils, and comprised of genes involved in the adaptive immune response (GO:0002250). By contrast, genes in cluster 4 were up-regulated in tumor neutrophils, and consisted of genes involved in chemokine-mediated signalling pathway (GO:0070098) and positive regulation of cellular metabolic process (GO:0031325). We observed several cellular metabolic processes were up-regulated, suggesting a change in the metabolic signature of neutrophils that infiltrate the tumor. In conclusion, the distinct metabolic signature led us to hypothesize that the pronounced glycolytic profile of tumor-infiltrating neutrophils mediates pro-tumoral activity and PDAC progression.
2022-12-31 | GSE114504 | GEO
Project description:Generation of organ-infiltrating neutrophils occurs in hematopoietic tissues and organs, such as bone marrow and spleen, in response to tumor- and host-derived factors. The de novo expanded neutrophils then egress from hematopoietic sites, circulate through the blood vessels and infiltrate into the organ interstitia and parenchyma. During above trafficking process, neutrophils can undergo phenotypic and functional changes in response to tissue environments. To determine the difference among neutrophils residing in the hematopoietic site—BM, circulating in the blood, and those infiltrating in the metastatic organ, the transcriptional profiles of neutrophils were analyzed by RNA sequencing. 4T1 cells were injected into the fourth mammary fat pads of female syngeneic BALB/cJ mice (8-week-old, n = 3). At day 10 (pre-metastatic stage), the mice were euthanized and then CD45+CD11b+Ly6G<high>Ly6C<med> neutrophils from bone marrow (BM), peripheral blood (PB) and lung were isolated by fluorescence-activated cell sorting. Total RNA was isolated from neutrophils using the miRNeasy Mini kit (Qiagen) and the transcriptional profiles of neutrophils were analyzed by RNA sequencing
2020-07-24 | E-MTAB-9128 | biostudies-arrayexpress
Project description:To investigate the difference among neutrophils circulating in the blood, and those infiltrating in the metastatic organ, we isolated peripheral blood (PB) and lung neutrophils from AT3 tumor-bearing mice. Total RNA was isolated from neutrophils and the transcriptional profiles of neutrophils were analyzed by RNA seq.
2022-12-12 | E-MTAB-12365 | biostudies-arrayexpress
Project description:In CUMS mice, neutrophils can infiltrate brain parenchyma and induce neuroinflammatory responses. To identify potential mediators, we analyzed the gene expression profiles of bone marrow neutrophils from mice subjected to CUMS and compared them with those of control mice. Interestingly, among the genes notably associated with neutrophil functions were Elane and Mpo, the crucial granule proteins of neutrophils that mediate chronic inflammation. Our study demonstrated that neutrophil-specific Elane knockout reduced neutrophil infiltration into the brain parenchyma and alleviated neuroinflammation. Elane plays a critical role in modulating the influence of peripheral neutrophils on brain.
2024-12-17 | GSE271724 | GEO
Project description:Elevated frequencies of GM-CSF-producing helper T (TH) cells are consistently found in multiple sclerosis (MS) patients and GM-CSF expression is a non-redundant feature of pathogenic TH cells in preclinical models of MS. GM-CSF activates an inflammatory signature in monocytes, and their progeny are the most abundant cellular infiltrate in acute MS lesions. To model deregulated GM-CSF levels, we generated a transgenic mouse line allowing the induction of GM-CSF expression in mature, peripheral TH cells. This antigen-independent GM-CSF release induced severe neurological deficits with almost 100% penetrance, accompanied by the infiltration of inflammatory monocyte-derived myeloid cells into the brain stem and spinal cord. Other organs did not show obvious signs for clinical pathology, despite also being infiltrated by inflammatory myeloid cells. We aim to unravel differences between organs, their responses and also the potential of tissue destruction by infiltrating cells by sequencing inflammatory myeloid cells isolate from the individual organs.
2017-02-21 | E-MTAB-5412 | biostudies-arrayexpress
Project description:miR-193b-3p and miR-365-3p expression values are increased in pancreas infiltrating neutrophils and basophils of new-onset diabetic NOD mice. We performed CITE-sequencing technology to investigate their phenotype and frequency. Using differentially expressed gene (DEGs) analysis, we further compared the different transcriptome profiles of pancreas infiltrating versus blood circulating neutrophils and basophils in new-onset diabetic NOD mice.
2023-09-20 | GSE214031 | GEO
Project description:The aim of this study was to investigate the role of infiltrating macrophages in renal allograft fibrosis. Forty-six protocol renal allograft biopsies obtained one-year after transplantation were stained with Sirius Red to quantify fibrosis and double stained with CD68 and CD206 to identify the proportion of alternately activated (M2) macrophages. 23 protocol biopsies obtained 12 months post transplant were analyzed for gene expression by microarray, which was correlated with macrophage infiltration and the severity of fibrosis. Phenotypic analysis showed 92% of infiltrating macrophages exhibited an M2 phenotype with CD68+CD206+ dual staining. Gene microarrays demonstrated a distinct alloimmune response despite the lack of rejection and inflammatory infiltrate with upregulation of interferon-γ-response genes. This suggests that following initiation of Th1 driven macrophage proliferation or infiltration, M2 macrophages contribute to tubular injury and progression of fibrosis. 23 protocol renal biopsies were obtained from patients at 12 month post transplant. The study population was divided into two groups according to the number of infiltrating macrophages (CD68 positive cells) (Group I: Recipients with a low number of infiltrating macrophages, CD68 positive cells < 400/mm2; Group II: Recipients with a high number of infiltrating macrophages, CD68 positive cells ≥ 400/mm2). Additional analyses were undertaken by dividing the group into those with fibrosis (ci score >1) and those without. To correlate gene expression with kidney fibrosis, or intensity of CD68 infiltrate, Spearman correlations analysis of the gene expression data with 12 month IFTA was performed and the correlation co-efficiency and its p value calculated. Gene Ontology enrichment and IPA pathway and network analysis (Ingenuity System Inc.) were performed on the associated genes. All p-values were two-sided, and p < 0.05 was considered significant.
2015-01-28 | E-GEOD-65326 | biostudies-arrayexpress
Project description:Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion. In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC) xenograft model to explore gene expression changes in situ in invading glioma cells compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex. Replicate sets of mice (n=4) were inoculated with either of two different GSC's derived from from human glioma, and each mouse had samples taken from the tumor mass, the infiltrating area and the mouse brain parenchyma, resulting in 3 samples per animal. The tumor mass and infiltrating samples were hybridized on human U133Plus2 Arrays, whereas the infiltrating samples and mouse brain parenchyma were hybridized on mouse
2014-02-20 | E-GEOD-53717 | biostudies-arrayexpress
Project description:This experiment was designed to compare the RNA expression profile in resting (control) neutrophils vs. that of TENs (neutrophils purified from tumor-bearing mice). In addition, we also compared the expression profiles of cultured neutrophils in vitro and treated with CCL2, CCL5 and GCSF. Circulating neutrophils were purified from control and 4T1 tumor-bearing mice and flash frozen. For in vitro cultures, circulating neutrophils were purified from control mice, cultured in the presence of chemokines for 2 hours and flash frozen.
2011-07-24 | E-GEOD-30887 | biostudies-arrayexpress
Project description:Breast cancer cells display preferences for specific metastatic sites including the bone, lung and liver. Metastasis is a complex process that relies, in part, on interactions between disseminated cancer cells and resident/infiltrating stromal cells that constitute the metastatic microenvironment. Distinct immune infiltrates can either impair the metastatic process or conversely, assist in the seeding, colonization and growth of disseminated cancer cells. Using in vivo selection approaches, we previously isolated 4T1-derived breast cancer cells that preferentially metastasize to these organs and tissues. In this study, we examined whether the propensity of breast cancer cells to metastasize to the lung, liver or bone is associated with and dependent on distinct patterns of immune cell infiltration. Immunohistocytochemistry and immunohistofluorescence approaches were used to quantify granulocytic infiltrates within distinct metastases and depletion of Gr1+ cells was performed to functionally interrogate the role of myeloid/granulocytic infiltrates in promoting metastasis to these organs. We show that T lymphocytes (CD3+), myeloid-derived/granulocytic cells (Gr-1+) cells and neutrophils (NE+) exhibit the most pronounced recruitment in lung and liver metastases, with markedly less recruitment within bone metastatic lesions. Interestingly, these infiltrating cell populations display different patterns of localization within soft tissue metastases. T lymphocytes and neutrophils are localized around the periphery of liver metastases whereas they were dispersed throughout the lung metastases. Furthermore, Gr-1+ cell-depletion studies demonstrate that infiltrating myeloid-derived/granulocytic cells, including neutrophils, are essential for the formation of breast cancer liver metastases but dispensable for metastasis to the lung and bone. Finally, we demonstrate that neutrophils that infiltrate and surround the liver metastases are polarized towards an N2 phenotype, which have previously been shown to enhance tumor growth and metastasis. Our results demonstrate that the liver metastatic potential of breast cancer cells is heavily reliant on interactions with infiltrating myeloid/granulocytic cells in the liver microenvironment.
2015-03-20 | GSE62598 | GEO