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Multiomics Analyses Unveil Immune Landscape in Pediatric and Adult Sepsis [scRNA_seq]

ABSTRACT: Sepsis is a leading cause of global mortality, characterized by organ dysfunction due to a dysregulated immune response to infection. This study aims to delineate the immune landscape in sepsis through single-cell RNA sequencing (scRNA-seq). A total of 133 samples were analyzed, including PBMCs from healthy adults, adult ICU controls, adult sepsis patients, healthy children, pediatric ICU controls, and pediatric sepsis patients. The scRNA-seq analysis revealed both common and unique immune cell populations across different infection sources and between adults and children. These findings provide insights into the pathophysiology of sepsis and suggest potential targets for personalized therapeutic approaches.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279452 | GEO | 2025/09/28

REPOSITORIES: GEO

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Project description:Genome wide DNA methylation profiling of isolated monocyte samples from healthy Kenyan children, the same children during an episode of acute malaria, healthy Kenyan adults, and healthy adults from the United States. The Illumina Infinium MethylationEPIC BeadChip microarray was used to obtain DNA methylation profiles across approximately 860,000 CpGs in negatively selected monocyte samples. Samples included monocytes from 8 children from western Kenya obtained while healthy and matching samples from the same 8 Kenyan children obtained during an episode of acute uncomplicated Plasmodium falciparum malaria, 8 healthy malaria-immune adults from western Kenya, and 8 healthy malaria-naive adults from the US. Abstract -- Background: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results: We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions: These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

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Multiomics Analyses Unveil Immune Landscape in Pediatric and Adult Sepsis [scRNA_seq]

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