A pairwise cytokine code explains the organism-wide response to sepsis [Spatial transcriptomics by Array-seq]
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ABSTRACT:
PROVIDER: PRJNA1046430 | ENA |
REPOSITORIES: ENA
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Project description:A pairwise cytokine code explains the organism-wide response to sepsis
| PRJNA929971 | ENA
Project description:A pairwise cytokine code explains the organism-wide response to sepsis [spatial transcriptomics by Visium]
| PRJNA929973 | ENA
Project description:A pairwise cytokine code explains the organism-wide response to sepsis [Whole-tissue RNA-seq]
| PRJNA929947 | ENA
Project description:Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the molecular and cellular impact of sepsis across organs remains rudimentary. Here, we characterize the pathogenesis of sepsis by measuring dynamic changes in gene expression across organs. To pinpoint molecules controlling organ states in sepsis, we compare the effects of sepsis on organ gene expression to those of 6 singles and 15 pairs of recombinant cytokines. Strikingly, we find that the pairwise effects of tumor necrosis factor plus interleukin (IL)-18, interferon-gamma or IL-1 suffice to mirror the impact of sepsis across tissues. Mechanistically, we map the cellular effects of sepsis and cytokines by computing changes in the abundance of 195 cell types across 9 organs, which we validate by whole-mouse spatial profiling. Our work decodes the cytokine cacophony in sepsis into a pairwise cytokine message capturing the gene, cell and tissue responses of the host to the disease.
2024-01-08 | GSE224145 | GEO
Project description:Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the molecular and cellular impact of sepsis across organs remains rudimentary. Here, we characterize the pathogenesis of sepsis by measuring dynamic changes in gene expression across organs. To pinpoint molecules controlling organ states in sepsis, we compare the effects of sepsis on organ gene expression to those of 6 singles and 15 pairs of recombinant cytokines. Strikingly, we find that the pairwise effects of tumor necrosis factor plus interleukin (IL)-18, interferon-gamma or IL-1 suffice to mirror the impact of sepsis across tissues. Mechanistically, we map the cellular effects of sepsis and cytokines by computing changes in the abundance of 195 cell types across 9 organs, which we validate by whole-mouse spatial profiling. Our work decodes the cytokine cacophony in sepsis into a pairwise cytokine message capturing the gene, cell and tissue responses of the host to the disease.
2024-01-08 | GSE224127 | GEO
Project description:Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the molecular and cellular impact of sepsis across organs remains rudimentary. Here, we characterize the pathogenesis of sepsis by measuring dynamic changes in gene expression across organs. To pinpoint molecules controlling organ states in sepsis, we compare the effects of sepsis on organ gene expression to those of 6 singles and 15 pairs of recombinant cytokines. Strikingly, we find that the pairwise effects of tumor necrosis factor plus interleukin (IL)-18, interferon-gamma or IL-1 suffice to mirror the impact of sepsis across tissues. Mechanistically, we map the cellular effects of sepsis and cytokines by computing changes in the abundance of 195 cell types across 9 organs, which we validate by whole-mouse spatial profiling. Our work decodes the cytokine cacophony in sepsis into a pairwise cytokine message capturing the gene, cell and tissue responses of the host to the disease.
2024-01-08 | GSE248904 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-08 | GSE224146 | GEO
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:Phospholipase A2 group V (PLA2G5) is a secretory and Ca2+-dependent lipolytic enzyme and is inducible during several pathologic conditions. However, it has been unknown how PLA2G5 plays a role in sepsis. To study the role of PLA2G5 in sepsis, we performed lipidomics analysis of plasma and tissues from LPS-injected mice with or without PLA2G5 blockade. Here, we showed that PLA2G5 is involved in the production of fatty acids such as oleic acid and linoleic acid, lysophospholipids such as lysophosphatidic acid, lysophosphatidylcholine, lysophatidylethanolamine, and lysophosphatidylserine species, and metabolites derived from polyunsaturated fatty acids such as arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and linoleic acids during sepsis. Thus, PLA2G5 regulates selective lipid pathways during sepsis.
2023-01-23 | ST002455 | MetabolomicsWorkbench
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