Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Promoting axon regeneration by enhancing the non-coding function of the injury-responsive coding gene Gpr151

ABSTRACT: Gene expression profiling in response to nerve injury has been mainly focused on protein functions of coding genes to understand mechanisms of axon regeneration and to identify targets of potential therapeutics for nerve repair. However, the protein functions of several highly injury-induced genes including Gpr151 for regulating the regenerative ability remain unclear. Here we present an alternative approach focused on non-coding functions of the coding genes, which led to the identification of the non-coding function of Gpr151 RNA interacting with RNA-binding proteins such as CSDE1. Gpr151 promotes axon regeneration by the function of its 5’- untranslated region (5’UTR) and expression of an engineered form of the 5’UTR improves regenerative capacity in vitro and in vivo in both sciatic nerve and optic nerve injury models. Our data suggest that searching injury-induced coding genes potentially functioning by their non-coding regions is required for the RNA-based gene therapy for improving axon regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE179145 | GEO | 2021/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Sciatic nerve injury-responsive differential CSDE1 association efficiency of ribosomal protein coding mRNAs

Project description:Gpr151 is an injury-responsive gene that promotes axon regeneration through its interaction with the 5'UTR region of its mRNA transcripts and the RNA-binding protein CSDE1. We found that knocking down or overexpressing the 5'UTR of Gpr151 changes the ribosomal protein mRNA regulon regulated by CSDE1. After the sciatic nerve injury, the association between the ribosomal protein mRNA regulon and CSDE1 was enhanced at dorsal root ganglions(DRGs), but this enhancement was not observed in the AAV-shGpr151 injected mice. Overexpression of 5'UTRmut, which has increased binding affinity to CSDE1, enhanced the ribosomal protein mRNA regulon and its association with CSDE1 in embryonic DRG neurons.

2023-08-18 | GSE236910 | GEO

Sciatic nerve injury-responsive differential mRNA profile and ribosome association efficiency of injury-induced mRNA

Project description:After nerve injury in the pheripheral nervous system, axon regeneration occurs through transcriptomic changes in neuronal cell bodies. To investigate which protein-coding transcripts are up-regulated and directed to ribosomes or not, we used RiboTag+/+;Advillin-Cre+ mice, expressing HA-tagged RPL22 specifically in sensory neurons, to profile their ribosome binding RNAs in nerve injured or uninjured dorsal root ganglion(DRG) tissues using HA-IP sequencing. We analyzed the results together with total RNA transcriptomics conducted under the same conditions. Through this analysis, we found mRNA of Gpr151 gene, one of the transcript that highly responds to injury but does not direct to the ribosomes, promoting axon regeneration by a non-coding RNA function.

2023-08-18 | GSE237046 | GEO

Promoting axon regeneration by enhancing the non-coding function of the injury-responsive coding gene Gpr151

Project description:Promoting axon regeneration by enhancing the non-coding function of the injury-responsive coding gene Gpr151

| PRJNA742408 | ENA

scRNAseq analysis of mouse L4 whole dorsal root ganglions with and without sciatic nerve crush injury

Project description:Peripheral sensory neurons with cell body in dorsal root ganglia (DRG) switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Studies of nerve injury responses in sensory neurons have revealed signaling and transcriptional mechanisms that increase their intrinsic regenerative capacity. However, the extent to which satellite glial cells (SGC), which completely surround the neuronal soma contribute to these responses remains unexplored. Using single cell RNA-seq, we defined the transcriptional profile of SGC in naïve and injured conditions and identified Fabp7, also known as BLBP, as a novel marker of SGC. We report that nerve injury elicits gene expression changes in SGC, which are mostly related to lipid metabolism, specifically fatty acid synthesis and the peroxisome proliferator-activated receptor (PPAR) signaling. Conditional deletion of Fatty acid synthase (Fasn), the key enzyme in de novo fatty acid synthesis, specifically in SGC, impairs axon regeneration. Treatment with fenofibrate, a PPARa agonist, rescues the impaired regeneration, suggesting that PPRAa, which belongs to a family of lipid regulated transcription factors, functions downstream of fatty acid synthesis in SGC to promote axon regeneration. These results unravel fatty acid synthesis in SGC as a fundamental novel mechanism mediating axon regeneration in mature peripheral nerves.

2020-08-23 | GSE139103 | GEO

MicroRNA-19a-PTEN axis is involved in the developmental decline of axon regenerative capacity in retinal ganglion cells

Project description:Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remains elusive. Here, we show that microRNAs are differentially expressed during RGC development, and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of PTEN, a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and increases axon extension in RGCs isolated from aged human donors. This uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity via intravitreal injection in patients with optic neuropathies.

2020-07-04 | GSE102458 | GEO

Transcriptional profiling of adult retinal ganglion cells during optic nerve regeneration

Project description:Objective: To identify genes that are differentially expressed in retinal ganglion cells undergoing axon regeneration after optic nerve injury. Adult mice that express cyan-fluorescent protein (CFP) in RGCs were treated with pro-regenerative treatment after optic nerve injury. The treated RGCs were selected by FACS (CFP+mcherry) and their RNA profiles were analyzed.

2020-12-29 | GSE142881 | GEO

Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun

Project description:After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during the chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes a significant clinical problem. We find that aging and chronically denervated repair cells express reduced c-Jun protein and the regenerative support provided by these cells is also reduced. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to that in controls. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. These experiments reveal that a common mechanism, reduced c-Jun in repair cells, underlies two major reasons for regeneration failure in the PNS. They underscore the central importance of Schwann cell c-Jun as a regulator of nerve repair, and point to molecular pathways that can be manipulated for improving the clinical outcome of nerve injuries.

2020-10-14 | E-MTAB-9640 | biostudies-arrayexpress

The molecular profile and ability to promote axon regeneration after peripheral nerve injury by Repair Schwann cells is distinctly different from that for developing Schwann cells

Project description:Since Schwann cells (SCs) support axonal growth at development as well as after peripheral nerve injury (PNI), developing SCs might be able to promote axon regeneration after PNI. The purpose of the current study was to elucidate the capability of developing SCs to induce axon regeneration after PNI. SC precursors (SCPs), immature SCs (ISCs), repair SCs (RSCs) from injured nerves, and non-RSCs from intact nerves were tested by grafting into acellular region of rat sciatic nerve with crush injury. Both of developing SCs completely failed to support axon regeneration, whereas both of mature SCs, especially RSCs, induced axon regeneration. Further, RSCs but not SCPs promoted neurite outgrowth of adult dorsal root ganglion neurons. Transcriptome analysis revealed that the gene expression profiles were distinctly different between RSCs and SCPs. These findings indicate that developing SCs are markedly different from mature SCs in terms of functional and molecular aspects and that RSC is a viable candidate for regenerative cell therapy for PNI.

2022-01-13 | GSE188399 | GEO

Changes in the coding/non-coding transcriptome and DNA methylome that define the Schwann cell repair phenotype after nerve injury

Project description:Schwann cell (Büngner) repair cells play a critical role in orchestrating nerve repair after injury, but the reprogramming process that generates them is poorly understood. We present the first combined whole genome coding and non-coding RNA and CpG methylation study after nerve injury. We show that genes involved in epithelial to mesenchymal transition are enriched in repair cells and we identify long non-coding RNAs in Schwann cells. We demonstrate that the AP-1 transcription factor c-Jun regulates the expression of certain micro RNAs in repair cells, in particular miR-21 and miR-34. Surprisingly, changes in CpG methylation are limited in injury, unlike development, and restricted to specific locations, such as enhancer regions of novel Schwann cell specific genes, such as Nedd4l, and near to local enrichment of AP-1 motifs. These epigenetic changes significantly broaden our understanding of Schwann cell reprogramming in peripheral nervous system tissue repair. To identify epigenetic regulators underlying successful nerve regeneration we generated RNA-Seq, small-RNA-Seq and whole genome bisulfite sequencing libraries for uninjured nerve versus three and/or seven day post nerve transection sciatic nerves of adult C57BL/6J mice crush.

2017-08-30 | E-MTAB-5633 | biostudies-arrayexpress

CELF RNA binding proteins promote axon regeneration in C. elegans and mouse through regulation of syntaxin

Project description:Axon injury triggers dramatic changes in gene expression. While transcriptional regulation of injury-induced gene expression is widely studied, less is known about the roles of RNA binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon regeneration. Using crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq) we identify a set of genes involved in synaptic transmission as mRNA targets of UNC-75. In particular, we show that UNC-75 regulates alternative splicing of two mRNA isoforms of the SNARE syntaxin/unc-64. In C. elegans mutants lacking unc-75 or its targets, regenerating axons form growth cones, yet are deficient in extension. Extending these findings to mammalian axon regeneration, we show that mouse Celf2 expression is upregulated after peripheral nerve injury and that Celf2 mutant mice are defective in axon regeneration. CLIP-seq and expression analysis also reveal CELF2 dependent regulation of selective syntaxins. Our data delineate a post-transcriptional regulatory pathway with a conserved role in regenerative axon extension.

2016-06-02 | GSE78111 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data