Systemic Inflammation Impairs Human Myelopoiesis
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ABSTRACT:
PROVIDER: PRJNA873943 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Systemic Inflammation Impairs Human Myelopoiesis [scRNA-Seq]
| PRJNA873948 | ENA
Project description:Systemic Inflammation Impairs Human Myelopoiesis [bulkRNA-Seq]
| PRJNA873949 | ENA
Project description:Systemic inflammation (SI) is a prevalent condition with a high mortality rate1. Survivors of hyperinflammatory state of SI frequently enter a long-lasting immunosuppressive state2 deteriorating their life quality3,4. Due to the extensive heterogeneity in SI etiology, the underlying mechanisms are not well understood. Here, we characterized the short and long-term effects of lipopolysaccharide (LPS)-induced SI (LPS-SI, also called endotoxemia5) on blood monocytes and bone marrow (BM) cells. Similar to clinical features of SI, we observed a profound but transient acute LPS response, followed by a long-term immunosuppressed state. Single-cell transcriptomic analysis of LPS-SI acute phase unveiled the loss of BM monocytes and the appearance of an inflammatory monocyte-like (i-Mono’s) population, expressing gene programs similar to a cell state identified in early-stage sepsis patients6. We observed impairment of myelopoiesis one week after LPS-SI manifested by a significant loss of intermediate and non-classical monocytes which is associated with reduced expression of interferon type I (IFN-I) genes. We confirm that this compromised myelopoiesis also happens in late-stage sepsis patients. Importantly, IFNb treatment reverted the LPS-induced immunosuppression in monocytes. Our results deepened the knowledge about SI and its long-lasting effects on myelopoiesis, substantiating the importance of IFN-I in the pathophysiology of SI-induced immunosuppression.
2025-03-15 | GSE212092 | GEO
Project description:Systemic inflammation (SI) is a prevalent condition with a high mortality rate1. Survivors of hyperinflammatory state of SI frequently enter a long-lasting immunosuppressive state2 deteriorating their life quality3,4. Due to the extensive heterogeneity in SI etiology, the underlying mechanisms are not well understood. Here, we characterized the short and long-term effects of lipopolysaccharide (LPS)-induced SI (LPS-SI, also called endotoxemia5) on blood monocytes and bone marrow (BM) cells. Similar to clinical features of SI, we observed a profound but transient acute LPS response, followed by a long-term immunosuppressed state. Single-cell transcriptomic analysis of LPS-SI acute phase unveiled the loss of BM monocytes and the appearance of an inflammatory monocyte-like (i-Mono’s) population, expressing gene programs similar to a cell state identified in early-stage sepsis patients6. We observed impairment of myelopoiesis one week after LPS-SI manifested by a significant loss of intermediate and non-classical monocytes which is associated with reduced expression of interferon type I (IFN-I) genes. We confirm that this compromised myelopoiesis also happens in late-stage sepsis patients. Importantly, IFNb treatment reverted the LPS-induced immunosuppression in monocytes. Our results deepened the knowledge about SI and its long-lasting effects on myelopoiesis, substantiating the importance of IFN-I in the pathophysiology of SI-induced immunosuppression.
2025-03-15 | GSE212091 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-03-15 | GSE212093 | GEO
Project description:Systemic inflammation halts lymphopoiesis and prioritizes myeloid cell production. How blood cell production switches from homeostasis to emergency myelopoiesis is incompletely understood. Here we show that Lymphotoxin-b receptor (LTbR) signaling in combination with TNF and IL1 receptor signaling in mesenchymal stem cells (MSCs) downregulates Il7 expression to shutdown lymphopoiesis during systemic inflammation. LTbR signaling in MSCs also promoted CCL2 production to enable inflammatory monocyte egress from the bone marrow. Furthermore, pharmacological or genetic blocking of Il7 downregulation in MSCs impaired myeloid cell production and egress, which reduced survival against systemic bacterial and viral infections. Interestingly, lymphotoxin a1b2 delivered by B-lineage cells, and specifically by mature B cells, contributed to promote Il7 downregulation and reduce MSC lymphopoietic activity. Our studies revealed an unexpected role for LTbR signaling in MSCs and identified mature B cells as an important regulator of emergency myelopoiesis.
2023-01-20 | GSE218505 | GEO
Project description:Systemic inflammation is reported to be associated with neutrophilic airway inflammation in asthma, this study aimed to examine the molecular mechanisms of the neutrophilia that is associated with systemic inflammation, and hypothesized that asthma patients with systemic inflammation have a group of genes that are differentially expressed and are assciated with airway inflammation. 50 asthma patients were recruited and grouped as asthmatics with systemic inflammation (n=18) and asthamtics without systemic inflammation (n=16) accroding to the levels of serum CRP and IL-6. RNA was extracted from induced sputum and was reverse-transcribed into cDNA. Gene profiling was performed using Illumina Sentrix HumanRef-8 Version 2 Expression BeadChips, and genes that were differentially expressed between asthmatics with systemic inflammation and asthmatics without systemic inflammation were compared and valided using qPCR.
2016-07-03 | E-GEOD-43397 | biostudies-arrayexpress
Project description:Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage
| PRJNA482564 | ENA
Project description:Skin microbiota affect systemic inflammation through mechanisms that have not been completely elucidated. We previously demonstrated that keratinocyte-specific IκBζ-deficient mice spontaneously develop autoimmune inflammation resembling human Sjögren syndrome. In this study, we examined how IκBζ-deficient epidermis dictates systemic autoimmune inflammation onset. To examine if IκBζ-deficient keratinocytes are susceptible to apoptotic stimuli in a steady state, we performed microarray analysis of untreated murine back epidermis. Data indicate that IκBζ-deficient epidermis is susceptible to environment antigens through apoptosis-related gene upregulation
2022-08-11 | GSE165515 | GEO
Project description:Genipin is a natural blue colorant in food industry. Inflammation is correlated with human disorders, and nuclear factor-κB (NF-κB) is the critical molecule involved in inflammation. In this study, the anti-inflammatory effect of genipin on the lipopolysaccharide (LPS)-induced acute systemic inflammation in mice was evaluated by NF-κB bioluminescence-guided transcriptomic analysis. Transgenic mice carrying the NF-κB-driven luciferase genes were administered intraperitoneally with LPS and various amounts of genipin. Bioluminescent imaging showed that genipin significantly suppressed LPS-induced NF-κB-dependent luminescence in vivo. The suppression of LPS-induced acute inflammation by genipin was further evidenced by the reductions of cytokine levels in sera and organs. Microarray analysis of these organs showed that the transcripts of 79 genes were differentially expressed in both LPS and LPS/genipin groups, and one third of these genes belonged to chemokine ligand, chemokine receptor, and interferon (IFN)-induced protein genes. Moreover, network analysis showed that NF-κB played a critical role in the regulation of genipin-affected gene expression. In conclusion, we newly identified that genipin exhibited anti-inflammatory effects in a model of LPSinduced acute systemic inflammation via downregulation of chemokine ligand, chemokine receptor, and IFN-induced protein productions. A total of 25 transgenic mice (female, 6 to 8 weeks old) were randomly divided into five groups of five mice: (1) mock, no treatment; (2) LPS (4 mg/kg), (3) LPS plus genipin (1 mg/kg), (4) LPS plus genipin (10 mg/kg), and (5) LPS plus genipin (100 mg/kg). Mice were challenged intraperitoneally with LPS and then with genipin 10 min later. Four hours later, mice were imaged for the luciferase activity, and subsequently sacrificed for ex vivo imaging, RNA extraction, and immunohistochemical staining.
2012-02-25 | E-GEOD-35934 | biostudies-arrayexpress