Similar Datasets
Project description:Diabetic neuropathy (DN) is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of DN, there are no specific treatments for DN and currently it is not possible to predict DN onset or progression. To examine gene expression signatures related to DN, microarray experiments were performed on a subset of human sural nerves collected during a 52-week clinical trial of acetyl-L-carnitine. A series of bioinformatics analyses analyzed differential gene expression and identified gene networks and pathways potentially responsible for the progression of DN. We identified 532 differentially expressed genes (DEGs) between patient samples with progressing or non-progressing DN, which were functionally enriched in pathways involving defense and inflammatory responses and lipid metabolism. A literature-derived co-citation network of the DEGs revealed gene sub-networks centered on apolipoprotein E (APOE), jun oncogene (JUN), leptin (LEP), serpin peptidase inhibitor E Type 1 (SERPINE1) and peroxisome proliferator-activated receptor gamma (PPARG). DEGs were used to predict DN progression in a test set of patients. Ridge-regression classification models with 14 DEGs achieved an overall accuracy of 92%, correctly classifying the progression status of 11 out of 12 patients. To our knowledge, this is the first study to identify transcriptional changes associated with DN progression in human sural nerves biopsies and describe their potential utility for molecular prediction of DN. Our results identifying the unique gene signature of patients with progressive DN will facilitate the development of new mechanism-based diagnostics and therapies. 18 progressor and 17 non-progressor at 52 weeks
2010-09-24 | E-GEOD-24290 | biostudies-arrayexpress
Project description:Multi-omic characterization of human sural nerves across polyneuropathies [Xenium]
| PRJNA1207203 | ENA
Project description:Diabetic neuropathy (DN) is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of DN, there are no specific treatments for DN and currently it is not possible to predict DN onset or progression. To examine gene expression signatures related to DN, microarray experiments were performed on a subset of human sural nerves collected during a 52-week clinical trial of acetyl-L-carnitine. A series of bioinformatics analyses analyzed differential gene expression and identified gene networks and pathways potentially responsible for the progression of DN. We identified 532 differentially expressed genes (DEGs) between patient samples with progressing or non-progressing DN, which were functionally enriched in pathways involving defense and inflammatory responses and lipid metabolism. A literature-derived co-citation network of the DEGs revealed gene sub-networks centered on apolipoprotein E (APOE), jun oncogene (JUN), leptin (LEP), serpin peptidase inhibitor E Type 1 (SERPINE1) and peroxisome proliferator-activated receptor gamma (PPARG). DEGs were used to predict DN progression in a test set of patients. Ridge-regression classification models with 14 DEGs achieved an overall accuracy of 92%, correctly classifying the progression status of 11 out of 12 patients. To our knowledge, this is the first study to identify transcriptional changes associated with DN progression in human sural nerves biopsies and describe their potential utility for molecular prediction of DN. Our results identifying the unique gene signature of patients with progressive DN will facilitate the development of new mechanism-based diagnostics and therapies.
2010-09-24 | GSE24290 | GEO
Project description:Multi-omic characterization of human sural nerves across polyneuropathies [snRNA-seq]
| PRJNA1207198 | ENA
Project description:Spinocerebellar ataxia type 3 (SCA3) is the most common dominantly inherited ataxia caused by a toxic gain-of-function CAG expansion in ATXN3. Currently, no effective preventive or disease-modifying treatments exist for this uniformly fatal disorder. This progressive, multisystem disorder is typified by neuronal degeneration and demyelination of critical parts of the central nervous system. Additionally, more than half of individuals with SCA3 also exhibit peripheral neuropathy symptoms like reduced limb sensation or burning pains, significantly impacting quality of life and contributing to mobility impairments. However, exploration into cell types and disease mechanisms underlying the SCA3 peripheral nervous system abnormalities remains limited by lack of comprehensive SCA3 animal model characterizations. This study employs the transgenic full-length human mutant ATXN3 YACQ84 (Q84/Q84) mouse to assess progression of sensorimotor behaviors, nerve conduction abnormalities, and ultrastructural features of neuropathy. Nerve conduction studies in Q84/Q84 mice show prominent sensorimotor nerve conduction velocity reductions in the sciatic and sural nerves and blunted signal amplitudes in the sural nerve, suggestive of axon loss and demyelination. Behaviorally, Q84/Q84 mice display abnormal responses to thermal and mechanical stimuli. Histological analysis of Q84/Q84 peripheral nerves reveals combined neuronal and glial pathology, characterized by loss of both large myelinated and small unmyelinated fibers, alongside demyelination pathologies. Bulk analyses of Q84/Q84 dorsal root ganglia and sciatic nerves revealed sensory neuropathy-related transcriptional and splicing dysregulation spanning diverse somatosensory pathways. Our results characterize significant peripheral neuropathy in a representative SCA3 mouse model, providing a strong foundation for future mechanistic and therapeutic studies of peripheral neuropathy in SCA3.
2026-05-11 | GSE320100 | GEO
Project description:Diseases of peripheral nerves termed polyneuropathies (PNPs) are common, mechanistically heterogeneous, and challenging to diagnose. Here, we integrated single nucleusi transcriptomics of peripheral nerves from 33 human PNP patients and four controls (365,708 nuclei) with subcellular spatial transcriptomics. We identified novel and human-specific nerve cell type markers including unexpectedly heterogeneous perineurial fibroblasts. All PNPs shared a loss of myelinating and an increase in repair Schwann cells and endoneurial lipid-associated macrophages. Transcriptional changes affected multiple cells outside of the endoneurium across PNPs, suggesting PNPs as ‘pan-nerve diseases’. Spatially, PNPs showed a previously unknown perineurial hyperplasia and fibrotic dispersion and this was most pronounced in immune-mediated PNPs. Single cell transcriptomics supported the differential diagnosis of PNPs with potential for future unbiased diagnostic classification.
2025-06-28 | GSE285984 | GEO
Project description:Gene expression profiling of sciatic nerves from rats with diabetic peripheral neuropathy
| PRJNA616271 | ENA
Project description:Although inflammation appears to play a role in neurolymphomatosis (NL), the mechanisms leading to degeneration in the peripheral nervous system are poorly understood. The purpose of this exploratory study was to identify molecular pathways underlying NL pathogenesis, combining clinical and neuropathological investigation with gene expression (GE) studies. Based on the neuropathic symptoms and signs, NL patients were classified into three forms of neuropathy: chronic symmetrical sensorimotor polyneuropathy (SMPN, n=3), multiple mononeuropathy (MN, n=4) and acute motor-sensory axonal neuropathy (AMSAN, n=1). Predominantly diffuse malignant cells infiltration of epineurium was present in chronic SMPN, whereas endoneurial perivascular cells invasion was observed in MN. In contrast, diffuse endoneurium malignant cells localization occurred in AMSAN. We identified alterations in the expression of 1266 genes, with 115 up-regulated and 1151 down-regulated genes, which were mainly associated with ribosomal proteins (RP) and olfactory receptors (OR) signaling pathways, respectively. Among the top up-regulated genes were actin alpha 1 skeletal muscle (ACTA1) and desmin (DES). Similarly, in NL nerves ACTA1, DES and several RPs were highly expressed, associated with endothelial cells and pericytes abnormalities. Peripheral nerve involvement may be due to conversion towards a more aggressive phenotype, potentially explaining the poor prognosis. The candidate genes reported in this study may be a source of clinical biomarkers for NL.
2022-09-16 | GSE213455 | GEO
Project description:Overall, 55 sural nerve biopsies from patients with CIDP (n=36) and CIDP-variants (n=18) were included into the study. Immunohistochemical analysis of the sural nerve specimens showed an aberrant deposition of terminal complement complex C5b-9 on endoneural capillaries in 52 (94%) of patients in addition to endoneural CD8+ T cell- and CD68+ macrophage infiltration. Gene expression studies showed an increase of factors C3 and C6 compared to NDCs with no difference in regard to clinical phenotype, whereas levels of IL6 or TNF-alpha were not significantly elevated. Our proteomic profiling approach revealed the statistically significant dysregulation of 50 proteins, which based on their respective functions suggest altered mitochondrial activity, perturbed cytoskeleton, and increased oxidative stress. The majority of patients with high to moderate complement deposition presented with a progressive disease course, however without any correlation with disease severity as measured by INCAT or MRC at baseline and follow-up. Our combined data supports the role of complement in CIDP pathogenesis. Based on these findings, we propose to further evaluate complement inhibition therapies as new targeted treatment option for patients with CIDP.
2025-09-29 | PXD056286 | Pride
Project description:Diseases of peripheral nerves termed polyneuropathies (PNPs) are common, mechanistically heterogeneous, and challenging to diagnose. Here, we integrated single nucleusi transcriptomics of peripheral nerves from 33 human PNP patients and four controls (365,708 nuclei) with subcellular spatial transcriptomics. We identified novel and human-specific nerve cell type markers including unexpectedly heterogeneous perineurial fibroblasts. All PNPs shared a loss of myelinating and an increase in repair Schwann cells and endoneurial lipid-associated macrophages. Transcriptional changes affected multiple cells outside of the endoneurium across PNPs, suggesting PNPs as ‘pan-nerve diseases’. Spatially, PNPs showed a previously unknown perineurial hyperplasia and fibrotic dispersion and this was most pronounced in immune-mediated PNPs. Single cell transcriptomics supported the differential diagnosis of PNPs with potential for future unbiased diagnostic classification.
2025-06-28 | GSE285983 | GEO