Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1106024 | ENA |
REPOSITORIES: ENA
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Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2023-12-22 | GSE251790 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2023-10-31 | GSE245661 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2024-01-24 | GSE254030 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2023-12-22 | GSE251872 | GEO
Project description:Autoimmunity is an established clinical feature in both Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and Post-Acute Sequelae of COVID (PASC). Passive transfer of immunoglobulins from patients' sera into mice induces some clinical features of PASC. IgG-induced transfer of disease phenotypes has long been appreciated, yet the exact mechanism of disease development remains largely elusive. Here, we show that IgG isolated from ME/CFS patients selectively induces mitochondrial fragmentation in primary human endothelial cells and alters mitochondrial energetics. Blocking IgG entry into cells using an Fc blocker inhibits the mitochondrial fragmentation phenotype. Both the digested Fab and Fc regions of IgG separately entered the endothelial cells. However, only the Fab fragment alone was able to alter the mitochondrial energetics, similar to native IgG. Proteomics analysis of IgG-bound immune complex revealed significant and specific changes within the immune complex of ME/CFS and PASC patients compared to healthy controls and other disease controls. We demonstrate that IgGs from ME/CFS patients carry a chronic protective response signal that promotes mitochondrial adaptation to stress through mitochondrial fragmentation, without altering mitochondrial ATP generation capacity in endothelial cells. Our results suggest that chronic and pathogenic IgG-induced mitophagy and metabolic alterations to stress-dependent ATP production may lead to cellular saturation, ultimately affecting mitochondrial health. These results provide an opportunity to develop alternative therapeutic intervention strategies.
2026-02-23 | PXD065439 | Pride
Project description:Although phosphorus is one of the most important essential elements for plant growth and development, the epigenetic regulation of inorganic phosphate (Pi) signaling is poorly understood. In this study, we identified the high-mobility-group protein OsHMGB1 as a key regulator of phosphate homeostasis and plant growth in rice (Oryza sativa). OsHMGB1 expression is induced by Pi starvation and encodes a nucleus-localized protein. Relative to wild-type plants, Oshmgb1 mutant plants had lower Pi content in their leaves, whereas plants overexpressing OsHMGB1 had higher Pi content, indicating that OsHMGB1 positively regulates Pi accumulation. Transcriptome deep sequencing and chromatin immunoprecipitation followed by sequencing showed that OsHMGB1 regulated the expression of a series of phosphate starvation responsive (PSR) genes by binding to their promoters. Furthermore, Assay for Transposase-Accessible Chromatin followed by sequencing revealed that OsHMGB1 was involved in maintaining chromatin accessibility. Indeed, OsHMGB1 occupancy positively correlated with genome-wide chromatin accessibility and gene expression levels. Notably, we determined that OsHMGB1 interacted with RNA polymerase II to help regulate transcription, especially under low Pi conditions. Taken together, our results suggest that OsHMGB1 functions as a transcriptional facilitator, revealing a key epigenetic mechanism to regulate Pi homeostasis and fine-tune plant acclimation responses to Pi-limited environments. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for HMG-GFP transgenic plants
2025-12-09 | GSE227770 | GEO
Project description:Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV. Given the distinct natures of the ventricles, we hypothesized that LV and RV-derived CFs would display baseline transcriptomic differences that influence their proliferation and differentiation following injury. Bulk RNA sequencing of CFs isolated from healthy left and right cardiac ventricles indicated that left ventricle-derived CFs may be further along the myofibroblast transdifferentiation trajectory than cells isolated from the right ventricle. Single-cell RNA-sequencing (scRNA-seq) analysis of the two populations confirmed that Postn+ CFs are more enriched in the LV, whereas Igfbp3+ CFs were enriched in the RV at baseline. Notably, following pressure overload injury, the LV developed a larger subpopulation of pro-fibrotic Thbs4+/Cthrc1+ injury-induced CFs, while the RV showed unique expansion of two less-well characterized subpopulations of CFs (Igfbp3+ and Inmt+). These findings demonstrate that LV and RV-derived CFs display baseline subpopulation differences that may dictate their diverging responses to pressure overload injury. Further study of these subpopulations will elucidate their role in the development of fibrosis and inform whether LV and RV fibrosis require distinct treatments.
2024-02-28 | GSE254914 | GEO
Project description:Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV. Given the distinct natures of the ventricles, we hypothesized that LV and RV-derived CFs would display baseline transcriptomic differences that influence their proliferation and differentiation following injury. Bulk RNA sequencing of CFs isolated from healthy left and right cardiac ventricles indicated that left ventricle-derived CFs may be further along the myofibroblast transdifferentiation trajectory than cells isolated from the right ventricle. Single-cell RNA-sequencing (scRNA-seq) analysis of the two populations confirmed that Postn+ CFs are more enriched in the LV, whereas Igfbp3+ CFs were enriched in the RV at baseline. Notably, following pressure overload injury, the LV developed a larger subpopulation of pro-fibrotic Thbs4+/Cthrc1+ injury-induced CFs, while the RV showed unique expansion of two less-well characterized subpopulations of CFs (Igfbp3+ and Inmt+). These findings demonstrate that LV and RV-derived CFs display baseline subpopulation differences that may dictate their diverging responses to pressure overload injury. Further study of these subpopulations will elucidate their role in the development of fibrosis and inform whether LV and RV fibrosis require distinct treatments.
2024-02-28 | GSE255542 | GEO
Project description:Although phosphorus is one of the most important essential elements for plant growth and development, the epigenetic regulation of inorganic phosphate (Pi) signaling is poorly understood. In this study, we identified the high-mobility-group protein OsHMGB1 as a key regulator of phosphate homeostasis and plant growth in rice (Oryza sativa). OsHMGB1 expression is induced by Pi starvation and encodes a nucleus-localized protein. Relative to wild-type plants, Oshmgb1 mutant plants had lower Pi content in their leaves, whereas plants overexpressing OsHMGB1 had higher Pi content, indicating that OsHMGB1 positively regulates Pi accumulation. Transcriptome deep sequencing and chromatin immunoprecipitation followed by sequencing showed that OsHMGB1 regulated the expression of a series of phosphate starvation responsive (PSR) genes by binding to their promoters. Furthermore, Assay for Transposase-Accessible Chromatin followed by sequencing revealed that OsHMGB1 was involved in maintaining chromatin accessibility. Indeed, OsHMGB1 occupancy positively correlated with genome-wide chromatin accessibility and gene expression levels. Notably, we determined that OsHMGB1 interacted with RNA polymerase II to help regulate transcription, especially under low Pi conditions. Taken together, our results suggest that OsHMGB1 functions as a transcriptional facilitator, revealing a key epigenetic mechanism to regulate Pi homeostasis and fine-tune plant acclimation responses to Pi-limited environments.
2025-12-09 | GSE227769 | GEO
Project description:Background: Cardiac fibroblasts (CFs) play a vital role in the physiological and pathological processes of the heart. Previous studies have demonstrated that high glucose stimulation induces the transformation of CFs into myofibroblasts, contributing to cardiac fibrogenesis. However, in vivo experiments have predominantly utilized adult animals, whereas most in vitro studies have focused on CFs derived from neonatal animals. The responses of CFs from different age groups to high glucose levels remain unclear. This study aimed to investigate transcriptional alterations in CFs at distinct developmental stages in response to high glucose exposure. Methods: CFs were isolated from neonatal (S1, 0–3 days), juvenile (S2, 3–4 weeks), adult (S3, 10–13 weeks), and aged (S4, 20 months) rats. CFs were exposed to normal (5.5 mM, NG) or high glucose (33 mM, HG). The cellular RNA was extracted for sequencing and analysis. Differentially expressed genes (DEGs) were validated by quantitative real-time PCR. Results: After NG treatment, fibrosis and inflammation-related gene expression in CFs (e.g., Col8a1, Col8a2, IL-6, Ccl2, Ccl20, Mmp2 and Mmp9) increased with age, while proliferation-related genes (MCM family, Sox10, Sox11) decreased. HG treatment most affected S3-CFs, showing 228 DEGs; it suppressed growth-related genes (Adra1d, Htr2b) and enhanced inflammatory genes (IL-6, Olr1). In S1-CFs, 197 inflammation-rich genes were upregulated under HG. S4-CFs displayed 166 DEGs, mostly metabolic downregulation (G6pc). S2-CFs had the fewest DEGs (112), focusing on cell metabolism. Conclusions: Fibrosis- and inflammation-associated gene expression in CFs showed an age-dependent stepwise elevation. CFs from distinct developmental stages responded differently to HG stimulation, with S3-CFs exhibiting the most pronounced response. These findings highlight the developmental characteristics of CFs and provide implications for the selection of appropriate CFs to investigate diabetes-associated cardiac fibrosis.
2025-02-04 | GSE269896 | GEO