Early Transcriptomic Response to Burn injury: Severe Burns are Associated with Immune Pathway Shutdown
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE182616 | GEO | 2021/10/31
REPOSITORIES: GEO
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Project description:Animal experiments were performed with male Sprague-Dawley rats (Charles River Laboratories, Boston, MA) weighing 150 ? 200 grams. All experimental protocols used in this study were approved by the Subcommittee on Research Animal Care, Massachusetts General Hospital. Rats were individually housed in a temperature-controlled (25oC) and light-controlled room (12h light-dark cycle) and allowed to adjust to their new surroundings for at least 5 days prior to the experiment. Water and rat chow were provided ad libitum to the animals. On the day of the treatment, the animals were randomly divided into two groups, burned and sham-burned. The burn injury consisted of a full-skin-thickness scald burn of the dorsum, calculated to be ~ 20% of the rat?s total body surface area (TBSA), induced by immersing the designated area in boiling water for 10 s (45). Rats were resuscitated with an intra-peritoneal injection of sterile saline solution (1.5 mL/Kg body weight/% TBSA) immediately after burn. The mortality rate of this treatment was negligible. At each time point (1, 2, 4, and 7d), three animals belonging to each group were sacrificed, the liver and serum collected, and stored at ?80oC after being inflicted with 20% TBSA burn injury. Sham-burn rats (n=3) considered as the control were treated identically except that they were immersed into a 37oC water bath and immediately sacrificed to collect the livers.
2007-11-03 | E-GEOD-1860 | biostudies-arrayexpress
Project description:Animal experiments were performed with male Sprague-Dawley rats (Charles River Laboratories, Boston, MA) weighing 150 ? 200 grams. All experimental protocols used in this study were approved by the Subcommittee on Research Animal Care, Massachusetts General Hospital. Rats were individually housed in a temperature-controlled (25oC) and light-controlled room (12h light-dark cycle) and allowed to adjust to their new surroundings for at least 5 days prior to the experiment. Water and rat chow were provided ad libitum to the animals. On the day of the treatment, the animals were randomly divided into two groups, burned and sham-burned. The burn injury consisted of a full-skin-thickness scald burn of the dorsum, calculated to be ~ 20% of the rat?s total body surface area (TBSA), induced by immersing the designated area in boiling water for 10 s (45). Rats were resuscitated with an intra-peritoneal injection of sterile saline solution (1.5 mL/Kg body weight/% TBSA) immediately after burn. The mortality rate of this treatment was negligible. At each time point (1, 2, 4, and 7d), three animals belonging to each group were sacrificed, the liver and serum collected, and stored at ?80oC after being inflicted with 20% TBSA burn injury. Sham-burn rats (n=3) considered as the control were treated identically except that they were immersed into a 37oC water bath and immediately sacrificed to collect the livers. Keywords = Burn Liver microarray genechip time course Keywords: time-course
2005-10-11 | GSE1860 | GEO
Project description:Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic co-morbidity and disease. To date, research has primarily focused on the systemic response severe injury, with little in the literature reported on impact of non-severe injuries (<15% total burn surface area; TBSA). To elucidate the metabolic consequences of non-severe burn injury, longitudinal plasma was collected from adults (n=35) who presented at hospital with a non-severe burn injury at admission, and at 6 week follow up. A cross-sectional baseline sample was also collected from non-burn control participants (n=14). Samples underwent multiplatform metabolic phenotyping using 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry to quantify 112 lipoprotein and glycoproteins signatures and 852 lipid species from across 20 subclasses.
Multivariate data modelling (Orthogonal projection to latent structures-discriminate analysis) revealed alterations in lipoprotein and lipid metabolism when comparing baseline control to hospital admission samples, with the phenotypic signature found to be sustained at follow up. Univariate (Mann-Whitney U) testing and OPLS-DA indicated specific increases in GlycB (p-value <1.0e-4), low density lipoprotein-2 subfractions (Variable importance in projection score; VIP >6.83e-1) and monoacyglyceride (20:4)(p-value <1.0e-4) and decreases in circulating anti-inflammatory high-density lipoprotein-4 subfractions (VIP >7.75e-1), phosphatidylcholines, phosphatidylglycerols, phosphatidylinositols and phosphatidylserines.
The results indicate a persistant systemic metabolic phenotype that occurs even in cases of non-severe burn injury. The phenotype is indicative of an accute inflammatory profile which continues to be sustained post-injury, suggesting an impact on systems health beyond the site of injury. The phenotypes contained metabolic signatures consistent with chronic inflammatory states reported to have elevated incidence post- burn injury. Such phenotypic signatures may provide patient stratification opportunities, to identify individual responses to injury, personalise intervention strtegies and improve acute care, reducing risk of chronic co-morbidity.
2023-07-19 | MSV000092486 | MassIVE
Project description:Rationale: Despite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm on the immune system. Few studies assessed hydrocortisone impact on the transcriptional response in shock, and we are lacking data in burns. Objectives: To assess the hydrocortisone-induced transcriptional modulation in severe burn shock, particularly on the immune response. Methods: We collected whole blood samples (n= 117) during a randomized controlled trial assessing the efficacy of hydrocortisone administration on burn shock. Using whole genome microarrays, we first compared burn patients from the placebo group (n=15) to healthy volunteers (n=13) to describe the transcriptional modulation induced by burn shock over the first week. Then we compared burn patients randomized for either hydrocortisone administration (n=15) or placebo (n=15) to assess hydrocortisone-induced modulation. Measurements and Main Results: Study groups were similar in terms of severity and major outcomes, but shock duration (significantly reduced in the hydrocortisone group). Many genes (n=2250) were differentially expressed between burn patients and healthy volunteers, with 85% of them exhibiting a profound and persistent modulation over seven days. Interestingly, we showed that hydrocortisone enhanced the shock-associated repression of adaptive, but also innate immunity. Conclusions: We found that the initial host response to burn shock encompasses a wide and persistent modulation of gene expression, with profound modulation of pathways associated with metabolism and immunity. Importantly, hydrocortisone administration may worsen the immunosuppression associated with severe injury. These data should be taken into account in the risk ratio of hydrocortisone administration in patients with inflammatory shock.
2017-07-02 | GSE77791 | GEO
Project description:Severe burn injury is a one of the most devastating forms of trauma with over 1.1 million burns each year requiring medical attention in the United States. Deaths from burn injury are commonly caused by immune-related sequelae such as pneumonia, organ failure and other opportunistic bacterial infections. Though there have been numerous studies to assess the immunological dysfunction associated with burn injury, there have yet to be a predictive biomarker, that can be used to assess high risk patients and their outcomes. We hypothesized that circulating extracellular vesicles (EVs) released early after burn injury would promote activate peripheral macrophages and specific cargo could be used as a biomarker to identify at-risk patients. To test this hypothesis, we assessed the immune consequences of adoptive transfer of EVs isolated after burn injury in vitro and used unbiased proteomic on EVs from mouse models and human burn patients from the UNC Jaycee Burn Center. Findings here suggest EVs serve as mediators of immune dysfunction and potential biomarkers.
2022-02-16 | PXD028515 | Pride
Project description:To understand the age-dependent response to burn injury, blood samples from pediatric and adult patients were collected at different times after severe burn injury. Gene expression was measured using Affymetrix U133 Plus 2.0 arrays for both patient samples and healthy controls. Time points were binned into two groups: early stage for <11 days and middle stage for 11-49 days. 114 arrays for 57 patients (2 time points per patient) and 63 arrays for 63 healthy controls.
2010-06-16 | E-GEOD-19743 | biostudies-arrayexpress
Project description:Neutrophils accumulate early in burn wounds, and their activation is associated with more severe burns. Understanding their functionality would facilitate the development of a more targeted therapeutic strategy for healing. However, we still lack a view of the cellular and functional heterogeneity in neutrophils involved in thermal injuries. Here, we establish the use of larval zebrafish for understanding neutrophil responses in burn. Zebrafish model allows for linking neutrophil states and their functions in real time through genetic modifications and live imaging. We performed single-cell transcriptional (scRNA-Seq) mapping of myeloid cells during a 3-day time course in burn and unwounded conditions. We identified transcriptionally distinct states in myeloid cells that form a consistent population structure across time points and conditions. By comparing burn and unwounded conditions, we found subtype-specific enrichment of biological processes and differential usage of gene regulatory networks. Pseudotime and RNA velocity analyses predict distinct branched trajectories for neutrophils, with one branch resembling the process of human neutrophil maturation. The other branch is not transcriptionally conserved with humans and is highly associated with leukocyte migration functionality, suggesting its engagement at the wound site. Transcriptional network analysis identified RAR/RXR family transcription factors as potential upstream factors driving this trajectory divergence in neutrophils. Furthermore, we characterized the transcriptional dynamics of cell-cell interactions in both conditions by time. Among burn-induced signaling pathways, we found il6-il6r signaling as a time-point-specific macrophage-neutrophil interaction, suggesting the importance of timing in innate immune response in burn. Finally, to test the translational value of our fish model, we examined zebrafish neutrophil state signatures in human burn patient samples. We found homolog expression of immature neutrophils positively correlates with the degree of total body surface area (TBSA) in patients. Flow cytometry confirmed the presence of neutrophils carrying these signatures in patient's blood. Our findings demonstrate the potential of using zebrafish as a model to identify early innate immune response signatures that could inform a timely treatment of burn in humans. This work builds the molecular foundation and a comparative single-cell genomic framework to guide future identification of actionable pathways to burn wound healing in patients.
2024-07-26 | GSE250610 | GEO
Project description:Early Transcriptomic Response to Burn injury: Severe Burns are Associated with Immune Pathway Shutdown
| PRJNA757018 | ENA
Project description:To understand the age-dependent response to burn injury, blood samples from pediatric and adult patients were collected at different times after severe burn injury. Gene expression was measured using Affymetrix U133 Plus 2.0 arrays for both patient samples and healthy controls. Time points were binned into two groups: early stage for <11 days and middle stage for 11-49 days.
2010-06-03 | GSE19743 | GEO
Project description:Type of experiment: Comparison of liver samples between sham (control) and 20% TBSA (total burn surface area) burn rats collected at 1h, 4h, 8h, and 24h. Experimental factors: Burn injury and time; Experiment design: All experimental liver samples collected after 1h, 4h, 8h, and 24h after burn injury were compared to a common reference (sham control treated as 0h time point); Bio source: Sprague-Drawley male rats weighing 150-200 g supplied through Charles river laboratories, MA (www.criver.com); Bio material manipulations: Rats (n=3 for each scald-burn and sham-burn time point) were individually housed in a temperature-controlled (25oC) and light-controlled room (12h light-dark cycle) and allowed to adjust to their new surroundings for at least 5 days prior to the experiment. Water and rat chow were provided ad libitum to the animals. On the day of the treatment, the animals were randomly divided into two groups, burned and sham-burned. The burn injury consisted of a full-skin-thickness scald burn of the dorsum, calculated to be ~ 20% of the ratâs total body surface area (TBSA), induced by immersing the designated area in boiling water for 10 s [Yamaguchi, 1997 #416]. Rats were resuscitated with an intra-peritoneal injection of sterile saline solution (1.5 mL/Kg body weight/% TBSA) immediately after burn. At each time point, three animals belonging to each group was sacrificed, the serum collected, and stored at â80oC. Hybridization extract: Total RNA was isolated from approximately 50 mg of pooled liver tissue using the Nucleospin II RNA isolation kit from Clontech (Palo Alto, CA), as per the manufacturerâs instructions. Labeling protocol: Labeling was performed as instructed by Affymetrix, Inc (www.affymetrix.com). In brief, 10 μg of total RNA was used for the double-stranded cDNA synthesis using the T7-oligo (dT) promoter primer kit (Affymetrix Inc.) and superscript RT II enzyme (Invitrogen). 1 μg of cDNA was labeled through invitro transcription reaction using T7 DNA polymerase in the presence of biotin labeled ribonucleotides. The cRNA was cleaned up using the Qiagen RNeasy columns following manufactures instructions. The cRNA (20 μg) was fragmented using the fragmentation buffer supplied as part of the Gene Chip Sample Cleanup Module (Affymetrix). Image analysis and raw data description: The images were analyzed using MAS V.0 software provided by Affymetrix, Inc. The raw data output consists of several metrices: Signal, Detection, Detection p-value, Stat pairs, Stat pairs used. Signal is a measure of the abundance of the transcript. Detection is call that indicates whether the transcript is detected (P, present), undetected (A, absent), or at the limit of detection (M, marginal). Detection p-value is a measure of the significance of the detection call. Stat pairs, is the number of probe pairs for a particular probe set on an array. Stat pairs used, is the number of probe pairs per probe set used in the analysis. Normalized and summarized data: All chips were scaled to a target intensity of 500 to account for differences between the replicate chips and their hybridization efficiencies using Affymetrix GENECHIP MAS V.0 software. The entire dataset is available at gene expression omnibus (http://www.ncbi.nlm.nih.gov/geo/) with the accession number GSE802. Three filters were serially used to obtain the list of annotated genes that demonstrated differential expression in intensity between sham and burn injured animals. In the first filter, only genes that were flagged as âpresentâ by the MAS V.0 analysis software in at least one of the time points in all replicate chips were considered for further analysis. This step eliminated all genes for which the expression data was not reproducible between the replicate chips. The genes that passed this criterion were subjected to a second filter where ANOVA was performed to test each gene independently for a statistical difference in expression between groups (0, 1, 4, 8 and 24 h). The output of the analysis is the probability (p value) that a difference in expression can be observed by chance i.e., probability of getting a false positive. While the occurrence of false positives can be controlled by choosing a higher significance level (0.01 or 0.001) it also concomitantly increases the false negatives. Therefore, in this study we have chosen to work with ANOVA p-value cut-off 0.05. To reduce the occurrence of the false positives, we have used the false discovery rate (FDR) method (33) which adjusts the ANOVA p-value (cut-off 0.05) while taking the dependencies between the genes into consideration. The 695 genes that demonstrated a significant ANOVA p-value were then selected and their expression values averaged. The third filter selected 339 genes that were either up-regulated or down-regulated by at least 2-fold between any one time point (1, 4, 8 or 24h) and the 0h time point (Sham control). To determine the temporal profiles in the data, gene expression values were hierarchically clustered using the dChip software (www.dChip.org). The expression values for a gene across all samples were standardized by setting the mean to 0 and standard deviation to 1. The software then builds a hierarchical cluster tree based on centroid-linkage method using Pearson correlation coefficient as the distance metric. A set of genes were assigned to cluster groups empirically based on visual inspection of their temporal expression patterns.
2007-10-11 | E-GEOD-802 | biostudies-arrayexpress