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Spatiotemporal Dynamics of Peripheral Immunity in OSA: A Single-Cell Atlas of the Genioglossus

ABSTRACT: We have employed a single cell sequencing approach using 10x Genomics scRNAseq to study genioglossus' immune environment underobstructive sleep apnea (OSA) condition. Genioglossusvis a key therapeutic target for OSA. Our study thus delineates a distinct spatiotemporal pattern of immune dysregulation, highlighting macrophages response as a potential key player in OSA-associated genioglossus injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE316894 | GEO | 2026/05/28

REPOSITORIES: GEO

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DNA methylation profiling in blood of OSA patients and controls

Project description:Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular morbidity and mortality. Epidemiological and animal models studies generate hypotheses for innovative strategies in OSA management by interfering intermediates mechanisms associated with cardiovascular complications. In this study, we interrogated DNA methylation profiles in 16 polysomnographically evaluated OSA patients (Apnea Hypopnea Index, AHI > 30) and 8 controls (AHI<5 events/h sleep). Blood samples were collected at initial visit (V1) and a year later (V2). OSA patients received Continuous Positive Air Pressure (CPAP) therapy with high adherence (> 4 hours/night). Control individuals did not receive CPAP therapy. Genomic DNA was treated with sodium bisulfite. Converted DNA was analyzed using Illumina’s Infinium Human Methylation 450 BeadChip assay. DNA methylation profiles enabled the prospective evaluation of inflammatory and epigenetics mechanism involved in cardiovascular complication of OSA patients compared with non OSA subjects, as well as the variation of epigenetic profiles in OSA patients after one year of high-adherence CPAP therapy.

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Epigenome analysis of peripheral blood mononuclear cell (PBMC) samples from obstructive sleep apnea patients and healthy subjects

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Single-cell RNAseq uncovers cellular heterogeneity and provides a signature for pediatric sleep apnea

Project description:Obstructive Sleep Apnea (OSA) is a highly prevalent disease and a major cause of systemic inflammation leading to neurocognitive, behavioral, metabolic, and cardiovascular dysfunction in children and adults. However, the impact of OSA on the heterogeneity of circulating immune cells remains to be determined. scRNA-seq demonstrated OSA-induced heterogeneity in cellular composition and enabled the identification of previously undescribed cell types in PBMCs.

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Effects of CPAP Therapy on Leukocyte Gene Expression

Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index ≥ 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures. Total RNA from peripheral blood leukocytes of 18 subjects with severe sleep apnea at baseline and after effective CPAP therapy was hybridized to 36 Affymetrix Genechip Human Gene 1.0 ST microarrays

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Project description:Pediatric obstructive sleep apnea (OSA) is a frequent respiratory disorder with an estimated prevalence of 3–6% in the general population. However, the underlying pathophysiology of OSA remains unclear. Recently, proteomic analysis using high-resolution and high-throughput mass spectrometry has been widely used in the field of medical sciences. In the present study, tandem mass tags (TMT)-based proteomic analysis was performed in the serum of patients with OSA.

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Project description:The role of exosomal miRNAs involved in the pathogenesis and development of pancreatic injury caused by obstructive sleep apnea (OSA) remains unclear. Here, miRNA sequencing (miRNA-seq) was used to investigate the expression profile of exosomal miRNAs in pancreatic tissue in a mouse model of chronic intermittent hypoxia (CIH) -induced pancreatic injury. A total of 55 newly predicted miRNAs and 277 existing miRNAs were identified in pancreatic tissue exosomes from the mouse model of chronic intermittent hypoxic-induced pancreatic injury. 3 up-regulated and 33 down-regulated miRNAs with differential expression were identified. 8 exosome-derived miRNAs were selected to construct CNC networks to predict target genes. Some targets and pathways were elucidated by GO analysis and KEGG analysis. Our work first comprehensively studied the expression profile of exosome-derived miRNA in pancreatic tissue of mouse models of OSA-induced pancreatic injury, bringing fresh perspectives on managing pancreatic injury brought on by OSA.

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DNA methylation profiling of blood monocytes in obstructive sleep apnea (OSA) patients: Effect of positive airway pressure (PAP) treatment.

Project description:Background: Obstructive sleep apnea (OSA) is a highly prevalent condition that is associated with a wide range of long-term morbidities including metabolic, cardiovascular, and cognitive alterations, possibly via activation of systemic inflammatory and oxidative stress pathways. Implementation of positive airway pressure (PAP) is the first line treatment for OSA. However, the molecular and cellular mechanisms underlying OSA-induced morbidities and their response to PAP treatment remain unclear. Methods And Results: DNA methylation profiles were examined in blood monocytes of OSA patients before and after PAP treatment. We identified 1,847 regions showing significant differential DNA methylation (p<0.001 and MAT score >4) between the groups. Analysis of biochemical pathways and gene networks demonstrated that differentially methylated regions (DMRs) were associated with immune responses, and particularly with mechanisms governing gene regulation by peroxisome proliferation-activated receptors (PPAR). Single locus quantitative PCR analysis revealed that DNA methylation was increased at the PPAR responsive elements (PPAREs) of 8 genes in the post-treatment samples, suggesting that PAP treatment leads to an increase in DNA methylation at PPAREs, possibly affecting the binding of the PPARG complex and downstream gene expression. Conclusions: Our work provides initial evidence of epigenetic regulation particularly involving metabolic pathways in OSA patients that are responsive to PAP treatment. We postulate that differentially methylated regions in blood monocytes may serve as potential biomarkers in clinical practice.

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