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Project description:Gene expression profile at single cell level from the liver of sham and sepsis mice
| PRJNA1171006 | ENA
Project description:Sepsis is an uncontrolled, systemic response to infection with life-threatening consequences. Our understanding of the pathogenesis of sepsis across organs of the body is rudimentary. Here, using mouse models of sepsis, we generate a dynamic, organism-wide map of the pathogenesis of the disease, revealing the spatiotemporal patterns of well-known and previously unrecognized effects of sepsis on the body. By combining functional perturbations with organism-wide profiling, we discover two interorgan mechanisms that are key to the pathophysiology of sepsis. First, we find that a hierarchical cytokine circuit arising from the pairwise effects of TNF plus IL-18, IFN-γ, or IL-1β suffices to explain a large fraction of the molecular effects of sepsis on the body. Moreover, the effects of these three cytokine pairs on the abundance of nearly two hundred cell types across nine organ types recapitulate half of all the cellular effects of sepsis. Second, we uncover an interorgan pathway whereby a gut-derived, secreted phospholipase, Pla2g5, mediates hemolysis in the blood circulation and contributes to multi-organ failure during sepsis. Thus, a simplifying principle in the systemic behavior of the cytokine network and a lipase misdirected from gut to blood provide fundamental insights to help build a unifying mechanistic framework for the pathophysiological effects of sepsis on the organ systems of the body.
2024-01-11 | GSE253061 | GEO
Project description:We investigated the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. Whole blood RNA sequencing analysis was performed on preoperative samples taken from 267 patients. These comprised patients who developed postoperative infection with (n=77) or without (n=49) sepsis, non-infectious systemic inflammatory response (n=31), or an uncomplicated postoperative course (n=110). Machine learning classification models built on preoperative transcriptomic signatures predicted postoperative outcomes including sepsis.
2024-08-30 | GSE208581 | GEO
Project description:We investigated the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. We built machine learning classification models on preoperative transcriptomic signatures to predict postoperative outcomes including sepsis. To test the predictive capability of these models for ongoing infection, whole blood RNA sequencing analysis on 61 independent patients with COVID-19 (10 mild, 51 severe cases) was performed.
2024-08-30 | GSE208587 | GEO
Project description:Lymphocytes are adversely affected during sepsis. Some CD4+ splenocytes undergo apoptosis while others become Th2 polarized. The molecular determinants of these phenotypic changes are not known. Here we compare the transcriptional response of septic CD4 splenocytes to CD4 splenocytes from sham-manipulated animals 6h after sepsis and identify an early transcriptional component to the septic CD4+ splenocyte phenotype. CD4+ splenocytes were isolated 6h after the surgical induction of sepsis for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain a homogeneous cell population in order to reduce any effects of cellular heterogeneity on expression profiles. To that end, immunomagnetic negative selection was used to enrich CD4+ splenocyte populations to ~91%. (n=5 biological replicates each CLP and sham)
2007-12-07 | E-GEOD-4479 | biostudies-arrayexpress
Project description:To describe the transcriptional changes associated with polymicrobial-sepsis induced myocardial depression in wild type and iNOS deficient mice. Keywords: myocardium, contractility, differential gene expression, nitric oxide synthase, infection We compared the transcriptional profile of C57/BL6 WT mice and congenic B6 129P2-Nos2tm1Lau/J mice after 48 hrs of polymicrobial sepsis induced by caecal ligation and perforation. 48 hours after surgery, mice were anaesthetised (intraperitoneal 100 mg/kg ketamine and 10 mg/kg xylazine). The right common carotid artery was cannulated (Millar Mikro-Tip pressure transducing catheter: 1.4F sensor, 2F catheter; Houston TX). Pressure tracings from the aorta and left ventricle were recorded (SonoLAB software; Sonometrics Corp., London Ontario Canada) and analysed using Cardiosoft and Origin 6.0 (Sonometrics Corp., and Microcal Software, Northampton MA). The heart was removed, emptied of blood, and snap frozen.
2010-11-17 | E-GEOD-9667 | biostudies-arrayexpress
Project description:Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection. This is best studied in humans and various mouse models, however finding sof these models to not always translate easy to the clinic. In order to improve this transfer, and because sepsis also plays a significant role in vetrenairy medicine, we use the pig as a model organism in sepsis research. We compare two modes of porcine sepsis iduction: fecal infusion and LPS infusion and also compare thse o wha we can find in mice
2023-12-31 | GSE250039 | GEO
Project description:we conducted integrative multiple levels of omics data including transcriptome, phosphoproteome, proteome and metabolome in different time-course of sepsis-associated liver dysfunction (SALD). This is the first trial to suggest the statistical pathway of integrative multi-omics data in sepsis. Given the increasing number of studies collecting multi-omics data but limited overview of the methodological framework for integrative analyses (Liu, Ding et al. 2013, Petersen, Zeilinger et al. 2014, Shah, Bonder et al. 2015), integrative approach in sepsis with liver dysfunction in this study will provide novel insights into the development of sepsis and ultimately offer new tools for overcoming the present diagnostic limitation. Therefore, a combined multi-omics dataset will give better accessibility of adoption in disease, and insight to identify the promising candidates for therapeutic strategies.
2023-06-21 | PXD025800 | Pride
Project description:To describe the transcriptional changes associated with polymicrobial-sepsis induced myocardial depression in wild type and iNOS deficient mice. Keywords: myocardium, contractility, differential gene expression, nitric oxide synthase, infection
2010-11-17 | GSE9667 | GEO
Project description:The temporal evolution of sepsis was monitored by transcriptional profiling of five critically ill children with meningococcal sepsis and sepsis-induced multiple organ failure. Blood was sampled at 6 time points during the first 48 hours of their admission to pediatric intensive care, where the children received standard clinical treatment including organ support and antimicrobial therapy. Striking transcript instability was observed over the 48 hours, with increasing numbers of regulated genes over time. Most notably, proposed biomarkers for sepsis risk stratification also showed expression instability, with varied expression levels over 48 hours. This study demonstrates the extent of the complexity of temporal changes in gene expression that occur during the evolution of sepsis-induced multiple organ failure. Importantly, stratification tools that propose expression of biomarkers must take into account the temporal changes, over the use of single snapshots that may be less informative.
2013-04-03 | E-MEXP-3850 | biostudies-arrayexpress