Glycation-mediated tissue-level remodeling of brain meningeal membrane by aging
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ABSTRACT:
PROVIDER: PRJNA892952 | ENA |
REPOSITORIES: ENA
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Project description:We performed bulk transcriptomic analysis to examine how glycation-modified collagen further impacts the function of meningeal fibroblasts. We preprocessed raw data to align bulk RNA-seq using STAR (detailed in Experimental Section) and identified differentially expressed genes (DEGs), especially ECM-related gene sets.
2022-10-26 | GSE216298 | 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: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.
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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.
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Project description:Social creatures must attend to threat signals from conspecifics and respond appropriately, both behaviorally and physiologically. In this work, we show a threat-sensitive immune signaling that orchestrates psychological processes and is amenable to social modulation. Repeated encounters with socially-cued threats triggered neutrophil priming preferentially in males. Meningeal niche-specific neutrophil activity was correlated with attenuated defensive responses to cues. The neutrophil-specific membrane protein CD177 responded to threat-predicting social cues, and its genetic ablation abrogated male behavioral phenotypes. Neutrophil CD177 signaling facilitated optimal meningeal IFN-γ production, which blunted neural response to threatening stimuli by enhancing intrinsic GABAergic inhibition within the prelimbic cortex. Initiation of meningeal neutrophil-mediated IFN-γ signaling was sensitized by negative emotional states and governed by socially dependent androgen release. This male-biased hormone/neutrophil regulatory axis is seemingly conserved in humans. Our findings provide insights into how immune responses influence behavioral responses to threats, suggesting a possible neuroimmune basis of emotional regulation.
2024-09-30 | GSE276662 | GEO
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
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