Temporal Changes in Macrophage Phenotype after Peripheral Nerve Injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA417027 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6252310.fastq.gz | Fastqsanger.gz | |||
| SRR6252311.fastq.gz | Fastqsanger.gz | |||
| SRR6252312.fastq.gz | Fastqsanger.gz | |||
| SRR6252313.fastq.gz | Fastqsanger.gz | |||
| SRR6252314.fastq.gz | Fastqsanger.gz |
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Project description:Identification of temporal changes in gene expression in macrophages isolated from the site of nerve injury.
2018-06-21 | GSE106488 | GEO
Project description:BackgroundMacrophages play a key role in peripheral nerve repair and demonstrate complex phenotypes that are highly dependent on microenvironmental cues.MethodsWe determined temporal changes in macrophage gene expression over time using RNA sequencing after fluorescence-activated cell sorting (FACS) macrophage populations from injured peripheral nerve. We identified key upstream regulators and dominant pathways using ingenuity pathway analysis and confirmed these changes with NanoString technology. We then investigate the effects of extreme polarizers of macrophage phenotype (IL4 and IFNγ) on nerve regeneration. We determined macrophage gene expression in vivo at the site of peripheral nerve injury with NanoString technology, and assessed recovery from sciatic nerve injury by cranial tibial muscle weights and retrograde labeling motor neurons in mice with deletion of IL4 or IFNγ receptors.ResultsWe demonstrate that IL4R and IFNγR deletions provide complementary responses to polarization, and alter expression of genes associated with angiogenesis and axonal extension, but do not influence recovery from peripheral nerve transection at 8 weeks after repair.ConclusionsOverall, this study provides a framework to evaluate the phenotype of macrophages over time, and provides a broader and more precise assessment of gene expression changes than has previously been commonly used. This data suggests ways in which polarization may be modulated to improve repair.
| S-EPMC6003127 | biostudies-literature
Project description:ChIP-seq of H3K27acetylation in sham and injured nerve. Schwann cells play an important role in the response of peripheral nerve to injury. This study was designed to identify enhancers that are altered in sciatic nerve at 3 days post-injury to help identify pathways that mediate the gene expression reprogramming that occurs in Schwann cells after nerve injury. We employed ChIP-seq analysis of H3K27 acetylation as a mark of actively engaged enhancers, and compared enhancers in the distal stump of transected sciatic nerve compared to contralateral (sham) condition.
2014-12-15 | GSE63103 | GEO
Project description:Systematic analyses of the temporal dynamics of transcriptomes and chromatin landscapes of macrophages during timecourse of TLR4-mediated inflammatory response. As a multifunctional effector cell, macrophages play pivotal roles in both the induction and resolution components of varied inflammatory processes. During the course of an inflammation response, macrophages engage in a homeostatic program characterized by tightly coordinated modulation of temporal outputs of both lipid metabolism and inflammation. We demonstrate inversely biphasic temporal dynamics of specific fatty acid metabolic and inflammatory gene expression profiles, associated with concordant temporal reprogramming of macrophage fatty acid profiles. In part, the late phase of the macrophage inflammatory response is characterized by tailoring of fatty acid related gene expressions, facilitating both significant induction of anti-inflammatory unsaturated fatty acid production and associated resolution of inflammation. We demonstrate the biphasic temporal dynamics of macrophage inflammation, specifically anti-inflammatory omega-3 and omega-9 unsaturated fatty acid levels, are transcriptionally driven genome-wide by an unexpected shift from an LXR to SREBP1-dominant regulatory program in the late phase inflammatory response. Collectively, our findings reveal a novel Srebp1-driven mechanism allowing the intimate inverse temporal relationship between the transcriptional regulation of inflammatory and fatty acid metabolic outputs; whereby modulation key transcriptional regulators (LXR, SREBP1 and NF-kB) of these pathways coordinate appropriate temporal tailoring of local enhancer associated reprogramming and eventual pathway regulatory interactions, during the course of TLR4-dependent inflammatory response in macrophages. This specific Srebp-driven, temporal reprogramming of macrophage fatty acid metabolism, characterized by late phase induction of anti-inflammatory unsaturated fatty acid production, is necessary for appropriate resolution of inflammation. Thus, this study suggests that selective reprogramming of macrophage lipid metabolism can serve as a viable therapeutic intervention aimed at ameliorating chronic inflammation and varied metabolic syndrome associated states.
2017-01-04 | GSE79423 | GEO
Project description:In vertebrates, the peripheral nervous system has retained its regenerative capacity, enabling severed axons to reconnect with their original synaptic targets. While it is well documented that a favorable environment is critical for nerve regeneration, the complex cellular interactions between injured nerves with cells in their environment, as well as the functional significance of these interactions, have not been determined in vivo and in real time. Here we provide the first minute-by-minute account of cellular interactions between laser transected motor nerves and macrophages in live intact zebrafish. We show that macrophages arrive at the lesion site long before axon fragmentation, much earlier than previously thought. Moreover, we find that axon fragmentation triggers macrophage invasion into the nerve to engulf axonal debris, and that delaying nerve fragmentation in a Wld(s) model does not alter macrophage recruitment but induces a previously unknown 'nerve scanning' behavior, suggesting that macrophage recruitment and subsequent nerve invasion are controlled by separate mechanisms. Finally, we demonstrate that macrophage recruitment, thought to be dependent on Schwann cell-derived signals, occurs independently of Schwann cells. Thus, live cell imaging defines novel cellular and functional interactions between injured nerves and immune cells.
| S-EPMC3324096 | biostudies-other
Project description:Foreign body reaction is one of the most important limiting factors to the clinical translation of implantable bioelectronics. The experiment compares the process of foreign body reaction, following the implantation of a silicon device in a mouse peripheral nerve, to that of peripheral nerve injury, following nerve crushing. Both processes are also compared to a naïve peripheral nerve from an uninjured mouse. The endpoints are day 1, 4, 7, 14 and 28 days.
2022-04-30 | E-MTAB-10294 | biostudies-arrayexpress
Project description:Peripheral nerve repair across long gaps remains clinically challenging despite progress made with autograft transplantation. While scaffolds that present trophic factors and extracellular matrix molecules have been designed, matching the performance of autograft-induced repair has been challenging. In this study, we explored the effect of cytokine mediated 'biasing' of macrophage phenotypes on Schwann cell (SC) migration and axonal regeneration in vitro and in vivo. Macrophage phenotype was successfully modulated by local delivery of either Interferon-gamma (IFN-?) or Interleukin-4 (IL-4) within polymeric nerve guidance channels, polarizing them toward pro-inflammatory (M1) or pro-healing (M2a and M2c) phenotypes, respectively. The initial polarization of macrophages to M2a and M2c phenotype results in enhanced SC infiltration and substantially faster axonal growth in a critically-sized rat sciatic nerve gap model (15 mm). The ratio of pro-healing to pro-inflammatory population of macrophages (CD206+/CCR7+), defined as regenerative bias, demonstrates a linear relationship with the number of axons at the distal end of the nerve scaffolds. The present results clearly suggest that rather than the extent of macrophage presence, their specific phenotype at the site of injury regulates the regenerative outcomes.
| S-EPMC3483037 | biostudies-literature
Project description:Peripheral nerve injury alters the expression of hundreds of proteins in dorsal root ganglia (DRG). Targeting some of these proteins has led to successful treatments for acute pain, but not for sustained postoperative neuropathic pain. The latter may require targeting multiple proteins. Since a single microRNA (miR) can affect the expression of multiple proteins, here, we describe an approach to identify chronic neuropathic pain-relevant miRs. We used two variants of the spared nerve injury (SNI): Sural-SNI and Tibial-SNI and found distinct pain phenotypes between the two. Both models induced strong mechanical allodynia, but only Sural-SNI rats maintained strong mechanical and cold allodynia, as previously reported. In contrast, we found that Tibial-SNI rats recovered from mechanical allodynia and never developed cold allodynia. Since both models involve nerve injury, we increased the probability of identifying differentially regulated miRs that correlated with the quality and magnitude of neuropathic pain and decreased the probability of detecting miRs that are solely involved in neuronal regeneration. We found seven such miRs in L3-L5 DRG. The expression of these miRs increased in Tibial-SNI. These miRs displayed a lower level of expression in Sural-SNI, with four having levels lower than those in sham animals. Bioinformatics analysis of how these miRs could affect the expression of some ion channels supports the view that, following a peripheral nerve injury, the increase of the 7 miRs may contribute to the recovery from neuropathic pain while the decrease of four of them may contribute to the development of chronic neuropathic pain. The approach used resulted in the identification of a small number of potentially neuropathic pain relevant miRs. Additional studies are required to investigate whether manipulating the expression of the identified miRs in primary sensory neurons can prevent or ameliorate chronic neuropathic pain following peripheral nerve injuries. To identify the miRs that were differentially dysregulated between Tibial-SNI and Sural-SNI, we first performed 12 microarrays in a limited number of samples (in four individual DRGs per group: Sham, Tibial-SNI and Sural-SNI; two L3-DRG and two L4-DRG). Then, miRs identified as having differential expression were corroborated with real time qRT-PCR in RNA isolated from individual DRGs (L3, L4 and L5) derived from 4 rats per group (not presented here, but in the manuscript).
2014-09-29 | E-GEOD-60033 | biostudies-arrayexpress
Project description:Peripheral nerve injuries are common in modern society. The patients may suffer from partial or total loss of sensory, motor and autonomic function in the involved segments of the body. However, The molecular mechanisms of the regeneration program has not yet been definitively clarified and the comprehensive lncRNA expression signature in peripheral nerve regeneration remains fully unknown.We performed a high throughput microarray assay to detect lncRNA expression profile in the distal end of peripheral nerve at 0,3,7,14 day after injury.
2015-10-17 | GSE74087 | GEO
Project description:Transcriptional changes are distinct in female and male mice in the time course of peripheral nerve injury response. Here, we present sexually dimorphic transcriptome profiles established in the space of 24 h period after sciatic nerve axotomy.
2022-07-18 | GSE182713 | GEO