Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA95443 | ENA |
REPOSITORIES: ENA
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Project description:Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for medicineâs future. Patients with injury severe enough to develop multiple organ dysfunction syndrome (MODS) are known to have multiple immune derangements, including T-cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly-enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers a previously unavailable opportunity to discover novel leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in the T-cell, monocyte, and total leukocyte transcriptome, with only 12% of these genomic changes common to all three cell populations. T-cell-specific pathway analyses identified increased gene expression of several novel inhibitory receptors (PD-1, CD152, NRP-1, Lag3), and concomitant decreases in stimulatory receptors (CD28, CD4, IL-2Rï¡). Functional analysis of T-cells and monocytes confirmed reduced T-cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly-enriched cell populations combined with knowledge-based pathway analyses leads to the identification of novel regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell specific pathway analyses can be used to discover novel pathway alterations in human disease. Experiment Overall Design: Type of experiment: Gene expression profiling of circulating total blood Experiment Overall Design: leukocytes, T-Cells, and Monocytes in severe trauma patients and healthy subjects. Experiment Overall Design: Experimental factors: Healthy subjects, 7 severely traumatized patients Experiment Overall Design: and 7 healthy subjects for transcriptome analysis. Venous blood samples Experiment Overall Design: were collected. Total blood leukocytes were isolated, and T-cell and Experiment Overall Design: monocyte populations were obtained from two subsequent aliquots of the Experiment Overall Design: leukocytes. Total leukocytes, enriched T-cells, and enriched monocytes were analyzed using Affymetrix GeneChip arrays. Experiment Overall Design: Number of hybridizations: 42 Human U133A GeneChip arrays (Affymetrix)
2008-06-13 | E-GEOD-5580 | biostudies-arrayexpress
Project description:Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for medicine’s future. Patients with injury severe enough to develop multiple organ dysfunction syndrome (MODS) are known to have multiple immune derangements, including T-cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly-enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers a previously unavailable opportunity to discover novel leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in the T-cell, monocyte, and total leukocyte transcriptome, with only 12% of these genomic changes common to all three cell populations. T-cell-specific pathway analyses identified increased gene expression of several novel inhibitory receptors (PD-1, CD152, NRP-1, Lag3), and concomitant decreases in stimulatory receptors (CD28, CD4, IL-2Ralpha). Functional analysis of T-cells and monocytes confirmed reduced T-cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly-enriched cell populations combined with knowledge-based pathway analyses leads to the identification of novel regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell specific pathway analyses can be used to discover novel pathway alterations in human disease. Keywords: Gene expression profiling of circulating total blood leukocytes, T-Cells, and Monocytes in severe trauma patients and healthy subjects.
2006-09-15 | GSE5580 | GEO
Project description:Purpose The aim of this study was to determine the fracture hematoma (fxH) proteome after multiple trauma using label free proteomics, comparing two different established surgical treatment strategies. Basic procedures A large animal (sus scrofa), multiple trauma animal model was used in which two different trauma surgical treatment methods were compared: Early Total Care (ETC) versus Damage Control Orthopedics (DCO). fxH was harvested after 72 hours and analyzed using liquid chromatography-tandem mass spectrometry. Protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Main findings The proteome of the early fxH was characterized by immunomodulatory and osteogenic proteins, as well as proteins involved in the coagulation cascade. Distinct, treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodeling. On the other hand, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodeling, as well as proteins related to anti-inflammatory and osteogenic processes. Principal conclusions The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after severe multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regenerative capabilities, and gained insights into regulatory mechanisms of fracture healing after severe trauma.
2024-05-24 | PXD049002 | Pride
Project description:Despite the high frequency of musculoskeletal extremity trauma, little is known about the dynamics of the initial inflammatory response that can result in pathologic healing. Here, we assess the circulatory monocyte/macrophage recruitment to sites of pathologic extremity wound healing as seen with heterotopic ossification (HO). Using single cell transcriptome analyses at key time points, we identify distinct monocyte/macrophage subpopulations that are recruited to the site of HO formation and contribute to ectopic bone development through varied transforming growth factor-1 (Tgfb1) expression. Monocyte/macrophage specific deletion of Tgfb1 leads to altered function of macrophages and reduced HO. We further identify CD47 as a novel target for Tgfb1 regulation on monocytes/macrophages as CD47 activation leads to decreased expression of Tgfb1 in macrophages and systemic treatment with CD47 activating peptide results in attenuation of canonical TGFB1 signaling and HO. These findings elucidate the critical role of monocytes/macrophage subpopulations in aberrant wound healing and provide a novel therapeutic avenue.
2019-10-23 | GSE126060 | GEO
Project description:Transcriptome Analyses of Heart and Liver Reveal Novel Pathways for Regulating Songbird Migration
| PRJNA480801 | ENA
Project description:Alterations in macrophage (Mφ) polarization, function and metabolic signature can foster development of chronic diseases, such as autoimmunity, or fibrotic tissue remodeling. Thus, identification of novel therapeutic agents that modulate human Mφ biology is crucial for treatment of such conditions. Herein we demonstrate that the soluble CD83 (sCD83) protein induces pro-resolving features in human monocyte-derived Mφ biology. We show that sCD83 strikingly increases the expression of inhibitory molecules including ILT-2 (immunoglobulin-like transcript 2), ILT-4, ILT-5 and CD163, whilst activation markers, such as MHC-II and MSR-1 were significantly downregulated. This goes along with a decreased capacity to stimulate alloreactive T cells in mixed lymphocyte reaction (MLR) assays. Bulk RNA sequencing and pathway analyses revealed that sCD83 downregulates pathways associated with pro-inflammatory, classically-activated Mφ (CAM) differentiation including HIF-1A, IL-6 as well as cytokine storm, whilst pathways related to alternative Mφ activation and Liver X receptor were significantly induced. By using the LXR pathway antagonist GSK2033, we show that transcription of specific genes (e.g. PPARG, ABCA1, ABCG1, CD36) induced by sCD83 are dependent on LXR activation. In summary, we herein reveal for the first time mechanistic insights into the modulation of human Mφ biology by sCD83, which is a further crucial pre-clinical study for the establishment of sCD83 as a new therapeutical agent to treat inflammatory conditions.
2023-12-14 | GSE245761 | GEO
Project description:Transcriptome analyses reveal epigenetic and radiation related genes in NSCLC cell
| PRJNA551680 | ENA
Project description:Transcriptomic analyses of renal allograft biopsies reveal conserved rejection signatures and molecular pathways
2020-11-17 | E-GEOD-9493 | ExpressionAtlas
Project description:Epigenome analyses reveal histone H4K20me3 and radiation related genes in NSCLC cell
| PRJNA551679 | ENA