Glycation-mediated tissue-level remodeling of brain meningeal membrane by aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE216298 | GEO | 2022/10/26
REPOSITORIES: GEO
Similar Datasets
Project description:Glycation-mediated tissue-level remodeling of brain meningeal membrane by aging
| PRJNA892952 | ENA
Project description:The goal of this study is to use bulk RNA-sequencing of the right brain hemisphere to observe the effects of TBI in the context of pre-existing meningeal lymphatic dysfunction in mice. We find that pre-existing meningeal lymphatic dysfunction potentiates the inflammatory response to TBI, suggesting an important role for the meningeal lymphatics in injury site drainage and proper recovery.
2020-07-25 | GSE155063 | GEO
Project description:Postnatal brain neurogenesis in mammals is believed to be restricted to rare germinative remnants of the neuroepithelium. In this study, we discovered that, in the postnatal brain, a subset of embryonically derived progenitors is present in meningeal substructures. These cells migrate from the meningeal substructures to the retrosplenial and visual motor cortex and differentiate into (electrically) functional integrated neurons. Lineage tracing analysis revealed that this subset of neural progenitors originate largely from PDGFR+ cells. PDGFR-derived cells differentiate mostly into Satb2+ neurons in cortical layers I-IV. Thus, a reservoir of embryonically derived progenitors in the meninges contributes to postnatal cerebral cortical neurogenesis.
2016-11-23 | E-MTAB-4951 | biostudies-arrayexpress
Project description:Glycation is a covalent protein modification that accumulates in the cellular environment. Histone proteins are particularly susceptible to glycation due to their extremely long half-lives and nucleophilic disordered tails. Here, we performed ATAC-seq on 293T cells cultured in the presence or absence of 0.5mM methylglioxal, a reactive glycolytic intermediate, for 12 hours. We demonstrate that methylglioxal treatment is associated with changes in histone occupancy and chromatin architecture globally.
2019-02-14 | GSE121252 | GEO
Project description:Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders and can modulate neurodevelopment and behavior. While this has sparked great interest in the meninges, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one week post-injury. Then, using bulk RNA sequencing, we assessed the differential long-term outcomes between young and aged mice following a TBI. In our scRNA-seq studies, we found that mild head trauma leads to an activation of type I interferon (IFN) signature genes in meningeal macrophages as well as the mobilization of multiple distinct sub-populations of meningeal macrophages expressing hallmarks of either classically activated or wound healing macrophages. We also revealed that dural fibroblasts in the meningeal compartment are highly responsive to TBI, and pathway analysis identified differential expression of genes linked to various neurodegenerative diseases. For reasons that remain poorly understood, the elderly are especially vulnerable to head trauma, where even mild injuries can lead to rapid cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges from mice that had received a mild TBI or Sham treatment 1.5 months prior. Notably, we found that aging alone induced massive upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited massive upregulation of immune-related genes and markedly reduced expression of genes involved in extracellular matrix remodeling and maintenance of cellular junctions. Overall, these findings illustrate the dynamic and complex transcriptional response of the meninges to mild head trauma. Moreover, we also reveal how aging modulates the meningeal response to TBI.
2022-12-22 | GSE206940 | GEO
Project description:Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders and can modulate neurodevelopment and behavior. While this has sparked great interest in the meninges, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one week post-injury. Then, using bulk RNA sequencing, we assessed the differential long-term outcomes between young and aged mice following a TBI. In our scRNA-seq studies, we found that mild head trauma leads to an activation of type I interferon (IFN) signature genes in meningeal macrophages as well as the mobilization of multiple distinct sub-populations of meningeal macrophages expressing hallmarks of either classically activated or wound healing macrophages. We also revealed that dural fibroblasts in the meningeal compartment are highly responsive to TBI, and pathway analysis identified differential expression of genes linked to various neurodegenerative diseases. For reasons that remain poorly understood, the elderly are especially vulnerable to head trauma, where even mild injuries can lead to rapid cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges from mice that had received a mild TBI or Sham treatment 1.5 months prior. Notably, we found that aging alone induced massive upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited massive upregulation of immune-related genes and markedly reduced expression of genes involved in extracellular matrix remodeling and maintenance of cellular junctions. Overall, these findings illustrate the dynamic and complex transcriptional response of the meninges to mild head trauma. Moreover, we also reveal how aging modulates the meningeal response to TBI.
2022-12-22 | GSE206932 | GEO
Project description:We show that NRF2 activation drives hepatocellular carcinoma development in vivo. Moreover, NRF2 undergoes glucose dependent modification called glycation and requires the de-glycating enzyme FN3K to maintain NRF2' oncogenic functions.
2019-06-22 | GSE133160 | GEO
Project description:Analysis of protein modifications is critical for quality control of therapeutic biologics. We used highly sensitive LC MS/MS analyses combined with multiple enzyme digestions to determine low abundance early-stage lysine glycation products of influenza vaccines derived from embryonated chicken eggs and cultured cells. A method utilizing chemoselective labeling of glycated lysine residues, through rapid conversion of site-specific glycation to stable N-ethylmaleimide derivatives at mildly acidic conditions, identified highly reactive lysine sites of proteins. As a result, we determined a widespread distribution of lysine modifications attributed by the region-selectivity and site-specificity of glycation toward influenza matrix 1, hemagglutinin and neuraminidase.
2024-10-17 | PXD052096 | Pride
Project description:Heterogeneity of meningeal cortical cells was deciphered on the molecular level using single cell RNA seq
2016-11-23 | GSE83948 | GEO
Project description:Understanding the effect of glycation on the function of transferrin, the systemic iron transporter, is fundamental to fully grasp the mechanisms leading to the loss of iron homeostasis observed in diabetes mellitus (DM). The spontaneous reaction with protein amino groups is one of the main causes of glucose toxicity, but the site specificity of this reaction is still poorly understood. Unbalance of iron metabolism has long been described in DM patients, and one of the main features is the occurrence of non-transferrin-bound iron in the blood serum. The presence of these toxic iron species is observed, despite low transferrin saturation levels. Here in, an in vitro approach was used to study human holo-transferrin glycation in detail. Holo-transferrin was incubated with increasing concentration of glucose (10; 20; 100 and 500 mM) and glycation sites were identified using nano-reverse phase – liquid chromatography coupled to high resolution mass spectrometry (nLC-MS). Overall 21 glycation hotspots were identified with lysine residues 103, 312 and 380 proving to be the most reactive sites. Glycation specificity was found to be remarkably different from that described for apo-transferrin.
2018-05-30 | PXD009345 | Pride