A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE70418 | GEO | 2015/10/06
SECONDARY ACCESSION(S): PRJNA288591
REPOSITORIES: GEO
Similar Datasets
Project description:The elderly are particularly susceptible to trauma, and their outcomes are frequently dismal. Such patients often have complicated clinical courses and ultimately die of infection and sepsis. Recent research has revealed that although elderly subjects have increased baseline inflammation as compared with their younger counterparts, the elderly do not respond to severe infection or injury with an exaggerated inflammatory response. Initial retrospective analysis of clinical data from the Glue Grant trauma database demonstrated that despite a similar frequency, elderly trauma patients have worse outcomes to pneumonia than younger subjects do. Subsequent analysis with a murine trauma model also demonstrated that elderly mice had increased mortality after posttrauma Pseudomonas pneumonia. Blood, bone marrow, and bronchoalveolar lavage sample analyses from juvenile and 20-24-mo-old mice showed that increased mortality to trauma combined with secondary infection in the aged are not due to an exaggerated inflammatory response. Rather, they are due to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an emergency myelopoietic response, engendering myeloid cells that fail to clear secondary infection. In addition, elderly people appeared unable to resolve their inflammatory response to severe injury effectively.
| S-EPMC4546902 | biostudies-literature
Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Analysis of the areas directly (spinal cord) and indirectly (raphe and sensorimotor cortex) affected by injury will help understanding mechanisms of SCI. Hypothesis: Areas of the brain primarily affected by spinal cord injury are the Raphe and the Sensorimotor cortex thus gene expression profiling these two areas might contribute understanding the mechanisms of spinal cord injury. Specific Aim: The project aims at finding significantly altered genes in the Raphe and Sensorimotor cortex following an induced moderate spinal cord injury in T9. Keywords: other
2005-02-11 | GSE2270 | GEO
Project description:Bone regeneration involves skeletal stem/progenitor cells within periosteum and bone marrow, the formation of a fibrous callus followed by the deposition of cartilage and bone matrix to consolidate the fracture. Interactions between bone and skeletal muscle are known to play a role in bone repair but the underlying mechanisms are poorly understood. To better understand the role of skeletal muscle during bone repair, we characterized stem/progenitor cells within skeletal muscle that participate in bone repair. We show that cells originating from bone marrow, periosteum and skeletal muscle are all derived from the Prx1 embryonic lineage. We developed a mouse polytrauma model combining a non-stabilized tibial fracture and mechanical injury to adjacent skeletal muscles. In this polytrauma model, bone fracture healing is impaired. We characterized the Prx1-derived cell population within skeletal muscle in response to fracture and to polytrauma. To do so, we performed fracture and polytrauma in Prx1Cre;Rosa mTmG mice. We harvested skeletal muscle surrounding the tibia at d0 (uninjured), and surrounding the fracture site at d3 and d5 post-fracture or post-polytrauma. Following enzymatic and mechanical digestion of skeletal muscle tissue, we FACS sorted Prx1-derived GFP+ cells and sequenced them using the 10X Chromium technology.
2021-03-04 | GSE164573 | GEO
Project description:The study was aimed to identify mechanisms linked to complicated courses after severe trauma by a systems biology approach. In severe trauma, overwhelming systemic inflammation can result in adverse events and the development of complications, including sepsis. In a prospective study, RNA samples from circulating leukocytes from patients with multiple injury (injury severity score ≥ 17) were analyzed for dynamic changes in gene expression over a period of 21 days by whole genome screening. Based on their clinical presentation, patients were divided into two subgroups: patients with secondary sepsis after trauma (n=5) and patients with systemic inflammation without infection (n=5). Expression cluster were defined by correlating gene expression data with clinical outcome parameters. Using unsupervised clustering, patients with systemic inflammation only and patients with sepsis showed a distinct expression pattern and the discrimination of clinical presentation was reflected by clustering of the samples. Explorative gene set analysis revealed robust upregulation of genes related to ‘hemoglobin metabolism/oxygen transport’ and ‘pathogenic E.coli infection’.
2015-11-01 | GSE70311 | GEO
Project description:The myeloid innate immune system plays key roles in the defence against parasites and bacteria, and carries out essential functions during tissue homeostasis and repair. It consist of neutrophils, macrophages, eosinophils, basophils and mast cells. Myelopoietic dysfunction or deregulation underlies numerous pathologies, ranging from immune deficiencies and allergies to myeloproliferative disorders and myeloid leukemia. To study malignant myelopoiesis, it is essential to understand the ontology of the different celltypes. In a generally accepted model for hematopoietic differentiation, all myeloid cells are preceded by a common granulocyte and macrophage progenitor that has the potential for all myeloid celltypes at the single cell level. However, we recently proposed a model for mouse hematopoiesis in which myeloid cells are formed via two independent pathways, one leading towards macrophages and neutrophils and one leading towards eosinophils, basophils and mast cells. The first pathway is affiliated with lymphoid potentials whereas the latter with megakaryocyte/erythroid development. Here, we demonstrate that those findings translate to human hematopoiesis. We demonstrate prospective isolation of myeloid progenitor cells that have restricted multipotent myeloid potential and are affiliated with lineages similar to those found in the mouse hierarchy.
2019-03-27 | GSE113046 | GEO
Project description:The study was aimed to identify mechanisms linked to complicated courses after severe trauma by a systems biology approach. In severe trauma, overwhelming systemic inflammation can result in adverse events and the development of complications, including sepsis. In a prospective study, RNA samples from circulating leukocytes from patients with multiple injury (injury severity score ⥠17) were analyzed for dynamic changes in gene expression over a period of 21 days by whole genome screening. Based on their clinical presentation, patients were divided into two subgroups: patients with secondary sepsis after trauma (n=5) and patients with systemic inflammation without infection (n=5). Expression cluster were defined by correlating gene expression data with clinical outcome parameters. Using unsupervised clustering, patients with systemic inflammation only and patients with sepsis showed a distinct expression pattern and the discrimination of clinical presentation was reflected by clustering of the samples. Explorative gene set analysis revealed robust upregulation of genes related to âhemoglobin metabolism/oxygen transportâ and âpathogenic E.coli infectionâ. 10 patients with multi-system trauma (ISS ⥠17 points) admitted to the Division of Trauma Surgery at the University Hospital Zurich were included. Whole blood from trauma patients was collected within the first 6 h after trauma (day 0) and on days 1, 2, 3, 5, 7, 10, 14, and 21. Total cellular RNA from circulating leukocytes was isolated using PaxGene Blood RNA Kit (PreAnalytix) for transcriptome profiling. RNA from blood of trauma patients was extracted and subjected to microarray analysis for comparison of longitudinal transcriptomic responses of patients. RNA samples of circulating leukocytes covering time points directly after admission (D0) and on the consecutive days (D1-D21) were subject to multifactorial microarray data analysis: Differences in dynamics of transcripts were assessed by contrasting time- and individual-resolved changes for sepsis and systemic inflammation without infection.
2015-11-01 | E-GEOD-70311 | biostudies-arrayexpress
Project description:We performed miRNA micro array to asses the miRNA profile differences in sEVs during inflammation vs. homeostatic conditions in endothelial cells. Therefore HUVEC cells were treated with a polytrauma cocktail comprised of IL1ß, IL6, CXCL8, C3a and C5a-des-Arg (PTC) at concentrations measured in patient serum 24hrs after polytrauma
2021-04-17 | GSE172211 | GEO
Project description:Physiological, anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. Contributor: The Inflammation and the Host Response to Injury Large Scale Collaborative Research Program Keywords: expression profiles
2009-04-13 | GSE11375 | GEO
Project description:Physiological, anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. Contributor: The Inflammation and the Host Response to Injury Large Scale Collaborative Research Program Keywords: expression profiles cRNA derived from whole blood leukocytes obtained within 12 hours of hospital admission provided gene expression data for the entire genome that were used to create a gene expression score for each patient. Expression profiles from healthy volunteers were averaged to create a reference gene expression profile which was used to compute a difference from reference (DFR) score for each patient. This score described the overall genomic response of patients within the first 12 hours following severe blunt trauma. Regression models were used to compare the association of the DFR, APACHE and ISS scores with outcome.
2009-04-12 | E-GEOD-11375 | biostudies-arrayexpress
Project description:Background: Trauma adjustment varies in children and adolescents. Studies on objective risk factors of posttraumatic stress symptoms (PTSS) yielded inconsistent results. Dysfunctional posttraumatic cognitions (PTCs) might play a mediating role between risk factors and posttraumatic symptomatology. Objective: To investigate the interplay of the characteristics of the trauma (e.g. trauma type), the characteristics of the individual (e.g. age, sex), and the characteristics of the social environment (e.g. parental distress, marital status) on PTSS and depression, taking the child's dysfunctional PTCs into account as a possible mediator. Method: Structural equation modelling was used to better understand trauma adjustment in two heterogeneous samples of children and adolescents: a sample of 114 participants aged 7-16 after accidental trauma and a sample of 113 participants aged 6-17 after interpersonal trauma. Results: In the accidental trauma sample, dysfunctional PTCs mediated the positive associations of younger age and lower parental educational level on child PTSS, but not on depression. In the interpersonal trauma sample, being female positively predicted child depression. Furthermore, parental dysfunctional PTCs positively predicted both child PTSS and depression. No mediation effect of child dysfunctional PTCs was found in the interpersonal trauma sample. Child dysfunctional PTCs moderately to strongly predicted child PTSS and depression in both trauma samples. Conclusions: The impact of the characteristics of the individual and the characteristics of the social environment on child PTSS and depression might depend on the type of trauma experienced. Dysfunctional PTCs mediated between the characteristics of the individual and the characteristics of the social environment and the severity of PTSS in the aftermath of accidental trauma, but not of interpersonal trauma.
| S-EPMC6493315 | biostudies-literature