Broad ultrastructural and transcriptomic changes underlie the multinucleated giant hemocyte mediated innate immune response against parasitoids
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PROVIDER: PRJNA750150 | ENA |
REPOSITORIES: ENA
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Project description:Multinucleated giant hemocytes (MGHs) represent a novel type of blood cell in insects that participate in a highly efficient immune response against parasitoid wasps involving isolation and killing of the parasite. Previously we showed that circulating MGHs have high motility and interaction with the parasitoid rapidly triggers encapsulation, structural and molecular mechanisms behind these processes remained elusive. Here, we use detailed ultrastructural analysis of MGHs and also live cell imaging to study encapsulation in Drosophila ananassae after parasitoid wasp infection. We found dynamic structural changes, mainly driven by the formation of diverse vesicular systems and a large variety of newly developed intracytoplasmic membrane organizations, moreover abundant generation of giant cell exosomes (GCE) in the MGHs. Moreover, we used RNA sequencing to study the transcriptomic profile of MGHs and the activated plasmatocytes 72 hours after infection, as well as the uninduced blood cells. This reveals that differentiation of MGHs is accompanied by broad changes in gene expression. Consistent with the observed structural changes, transcripts mainly related to vesicular function, cytoskeletal organization and adhesion were enriched in MGHs. In addition, transmembrane receptors were upregulated, which may be important for parasitoid recognition. Our results reveal coordinated molecular and structural changes in the course of MGH differentiation and parasitoid encapsulation, providing a mechanistic model for a powerful innate immune response.
2021-12-17 | GSE180960 | GEO
Project description:Osteoclast is the primary bone resorbing multinucleated cell. However, human osteooclastoma bone tumor derived osteoclat cellsare However, gene expression profile of giant osteoclat cells is unclear. Here, we performed gene expression profiling of enriched giant cells to elucidate the neoplastic effects and dynamic changes in gene expression responsible for abnormal hyperactive osteoclast formation in the tumor bone microenvironment.
2020-04-15 | GSE148616 | GEO
Project description:The role of placental macrophages is largely ignored in the success of pregnancy. We found that CD14+ macrophages purified from at-term placentas spontaneously matured into multinucleated giant cells (MGCs). MGCs lost the expression of CD14 and co-inhibitory molecules, such as Programmed cell Death-Ligands 1 and 2. Although MGCs kept phagocytosis and property to produce ROS, their inflammatory potential measured by TNF/IL-10 imbalance and activation of p38 MAPK and NF-M-NM-:B was blunted without being associated with M2 phenotype. The investigation of gene expression revealed the enrichment with categories related to inflammation, apoptosis and canonical functions of macrophages in MGCs. Whereas most of the genes associated with inflammation and immune responses were down-modulated, those such as VEGFC or associated with matrix remodeling were specifically up-regulated in MGCs. Importantly, we found that patients with preeclampsia or chorioamnionitis, two inflammatory and infectious pathologies, respectively, that affect placentas, were unable to generate MGCs. Taken together, these results suggest that MGCs represent a new way to regulate the inflammatory and cytocidal activity of placental macrophages in a context that imposes contradictory constraints, such as semi-allograft acceptance and defense against aggression. The dysregulation of MGC formation may be associated with placental inflammatory and infectious pathologies. Placental macrophages CD14+ were cultured for 9 days to form multinucleated giant cells (MGC). The transcriptome of MGCs was compared to the transcriptome of placental macrophages (CD14+)
2014-01-07 | E-GEOD-38747 | biostudies-arrayexpress
Project description:We characterized the mouse trophoblast giant cell epigenome and gene expression profiles. We then compared these data to our data on underrepresentation in the polyploid trophoblast giant cells. We profiled 5 histone modifications (+ chromatin input) using ChIP-Seq, and digital expression profiles (3' RNA-Seq) for trophoblast giant cells derived from mouse. Furthermore, we profiled digital expression profiles (3' RNA-Seq) for in vivo trophoblast giant cells samples from e9.5 wildtype mouse trophoblast giant cells. We found that underrepresented domains in trophoblast giant cells are enriched for repressive marks and anti-correlate with active marks and transcription.
2014-05-29 | E-GEOD-50561 | biostudies-arrayexpress
Project description:Monocytes/macrophages have the ability to fuse in multinucleated giant cells (MGCs). Except for osteoclasts that resorb bones on large surfaces, the function of other macrophage-derived MGCs, which appear under pathological situations associated with granulomatous inflammation such as tuberculosis, is not understood. Here we deciphered functions and gene expression profiles of MGCs obtained after stimulation of human monocytes with IFN-gM-BM- and concanavalin A. First, we show that the competence of MGCs in phagocytosis and O2- production was similar to those of monocytes-derived macrophages (MDMs) and that MGCs exhibited a M1 polarization. Second, we analyzed the transcriptional profile of MGCs using gene categories and the building of gene networks. The signature of MGCs was markedly distinct from that of resting or stimulated MDMs. It consisted of the up-regulation of genes involved in adhesion and cytoskeleton organization while genes associated with immune response were down-regulated. Hence, MGC formation was associated with a profound and original modulation of gene expression repertoire suggesting that macrophage immune were not prominent in MGC. This expression gene repertoire may be instrumental to understand the specific function of this giant macrophages in human pathologies 9 samples of monocytes-derived macrophages and 3 samples of mulitnucleated giant cells. 3 samples of MDM treated with concanavalin A, 3 samples of MDM treated with IFN-g, and 3 control MDM.
2012-12-07 | E-GEOD-30273 | biostudies-arrayexpress
Project description:To investigate the effects of macrophage cell fusion and multinucleation, we have sorted mononuclear and multinucleated macrophages from 3 types of polykaryons: osteoclasts, foreign body giant cells (FBGCs) and Langhans giant cells (LGCs).
2023-01-08 | GSE219114 | GEO
Project description:We characterized the mouse trophoblast giant cell epigenome and gene expression profiles. We then compared these data to our data on underrepresentation in the polyploid trophoblast giant cells.
2014-05-29 | GSE50561 | GEO
Project description:Giant cell myocarditis (GCM) is a rare, often rapidly progressive and potentially fatal, disease caused by T-cell-mediated cardiac inflammation that typically affects young and middle-aged adults. The detailed inflammatory response remained unknown, especially the formation of multinucleate giant cells.Methods and Results: Rats were treated with myosin heavy-chain-α peptides to generate a GCM model. We performed single-cell RNA sequencing analysis of 15,714 Cd45 + cells extracted from hearts from GCM rat model and normal rats. We identified 24 subclusters including macrophages, neutrophils, T cells and so on. The GCM was characteristic with macrophage cluster 1, neutrophil cluster 3, macrophage cluster 2, neutrophil cluster 1 and Th17 cells. Two specific macrophage clusters involved in the GCM have roles in phagocytosis, and NETosis was found to contribute into the process of GCM. Its receptor, Ccdc25 , expressed in the macrophage cluster 1 and Th17, suggesting that neutrophils could regulate other immune cells in GCM. Importantly, inhibitor of NETosis, GSK484, could alleviate the inflammation of GCM in vivo. Finally, MPO (a marker of neutrophils) and H3cit (a marker of NETosis) were expressed at higher levels in GCM patients than in DCM patients and healthy controls and neutrophils were part of multinucleated giant cells. IMC analysis revealed that the formation of multinucleate giant cells of GCM.Conclusions: We herein present a comprehensive single-cell landscape of the cardiac immune cells in GCM. In addition, we elucidated the contribution of NETosis to the pathogenesis of GCM, which may serve as a potential therapeutic target in the clinic.
2023-06-15 | GSE221111 | GEO
Project description:Giant cell granulomas of the jaws often occur sporadically as single central or peripheral lesions. They are characterized by KRAS, FGFR1, or TRPV4 somatic mutations, the latter occurring exclusively in the central form. Less commonly, multiple giant cell lesions can develop in the context of syndromes such as cherubism, which is an autosomal dominant bone disease. Morphologically, giant cell granulomas can closely resemble other giant cell-rich lesions such as non-ossifying fibroma and aneurysmal bone cyst, and to a minor extent giant cell tumour of bone and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and, recently, DNA methylation profile has been shown to be clinically useful for the diagnosis of other tumour types, including brain tumours as well as bone and soft tissue sarcomas. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic giant cell granulomas of the jaws and cherubism to test whether DNA methylation patterns can help to distinguish these entities. Additionally, we further compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. Our results showed that central and peripheral sporadic giant cell granulomas of the jaws and cherubism share a related DNA methylation pattern with that of peripheral sporadic giant cell granulomas and cherubism appearing slightly distinct, while central sporadic giant cell granulomas show overlap with both of the former. Non-ossifying fibroma, aneurysmal bone cyst, giant cell tumour of bone, and chondroblastoma, on the other hand, have distinct methylation patterns. Therefore, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions of the jaws. Conversely, it could discriminate sporadic giant cell granulomas from their giant cell-rich mimics.
2023-10-18 | GSE218252 | GEO
Project description:Co-culture of platelets with monocytes induces the forming of multinucleated giant foam cells (MP-Mac or MP-MNGCs). Compared with normal monocyte differentiated macrophages (M-Mac), the MP-MNGCs can engulf more mycobacteria with suppressed inflammatory responses (releasing more IL-10 with less TNF-gamma). Microarray analysis demonstrated that the MP-MNGCs greatly up-regulated CXCL5, PPBP, NT5E, PDPN, CXCL3 and other M2 related genes, such as ARG1, CXCL1, CD163, etc. GO analysis revealed higher cluster of genes in response to wounding and nuclear division. Immunohistochemistry studies indicated similar high expression of IL-10, CXCL5, CXCL3, PDPN and ARG1 expression in MNGCs of TB granuloma, which indicated that phagocytosis of activated platelets by monocytes might be involved in pathogenesis of TB granuloma. Microarray experiments were performed as dual-color hybridizations. To compensate for dye-specific effects, a dye-reversal color-swap was applied. Quality control and quantification of total RNA amount was assessed using an Agilent 2100 bioanalyzer (Agilent Technologies) and a NanoDrop 1000 spectrophotometer (Kisker).
2014-01-01 | E-GEOD-45960 | biostudies-arrayexpress