Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cytokine Polarized Bone Marrow Neutrophils Drive Axon Regeneration

ABSTRACT: The adult central nervous system (CNS) has a limited capacity for self-repair. Severed CNS axons typically do not regrow. There is an unmet need for treatments specifically designed to enhance neuronal viability, facilitate CNS axon regeneration, and ultimately restore lost neurological functions to individuals with traumatic CNS injury, multiple sclerosis, and stroke, among other disorders. Here we demonstrate that both mouse and human bone marrow (BM) neutrophils upregulate markers of alternative activation, and acquire the ability to promote neurite outgrowth, following polarization with a combination of recombinant interleukin-4 (IL-4) and granulocyte-colony stimulating factor (G-CSF). Moreover, adoptively transferring IL-4/G-CSF polarized BM neutrophils into experimental models of CNS injury resulted in significant axon regeneration within the optic nerve and spinal cord. The findings reported in this paper hold significant implications for the future development of autologous myeloid cell-based therapies that may bring us closer to effective solutions for reversing CNS damage.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE244934 | GEO | 2023/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Augmenting fibronectin levels in injured adult CNS promotes axon regeneration in vivo [bulk RNA-seq]

Project description:In an attempt to repair injured central nervous system (CNS) nerves/tracts, immune cells are recruited into the injury site, but endogenous response in adult mammals is insufficient for promoting regeneration of severed axons. Here, we found that a portion of retinal ganglion cell (RGC) CNS projection neurons that survive after optic nerve crush (ONC) injury are enriched for and upregulate fibronectin (Fn)-interacting integrins Itga5 and ItgaV, and that Fn promotes long-term survival and long-distance axon regeneration of a portion of axotomized adult RGCs in culture. We then show that, Fn is developmentally downregulated in the axonal tracts of optic nerve and spinal cord, but injury-activated macrophages/microglia upregulate Fn while axon regeneration-promoting zymosan augments their recruitment (and thereby increases Fn levels) in the injured optic nerve. Finally, we found that Fn’s RGD motif, established to interact with Itga5 and ItgaV, promotes long-term survival and long-distance axon regeneration of adult RGCs after ONC in vivo, with some axons reaching the optic chiasm when co-treated with Rpl7a gene therapy. Thus, experimentally augmenting Fn levels in the injured CNS is a promising approach for therapeutic neuroprotection and axon regeneration of at least a portion of neurons.

2024-06-28 | GSE269813 | GEO

Augmenting fibronectin levels in injured adult CNS promotes axon regeneration in vivo [scRNA-seq]

2024-06-28 | GSE269812 | GEO

Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo [Third party: scRNA-seq]

Project description:Nuclear factor erythroid 2 like (Nfe2l) gene family members 1-3 mediate cellular response to oxidative stress, including in the central nervous system (CNS). However, neuronal functions of Nfe2l3 are unknown. Here, we comparatively evaluated expression of Nfe2l1, Nfe2l2, and Nfe2l3 in singe cell RNA-seq (scRNA-seq)-profiled cortical and retinal ganglion cell (RGC) CNS projection neurons, investigated whether Nfe2l3 regulates neuroprotection and axon regeneration after CNS injury in vivo, and characterized a gene network associated with Nfe2l3 in neurons. We showed that, Nfe2l3 expression transiently peaks in developing immature cortical and RGC projection neurons, but is nearly abolished in adult neurons and is not upregulated after injury. Furthermore, within the retina, Nfe2l3 is enriched in RGCs, whereas Nfe2l1 and Nfe2l2 are expressed robustly in other retinal cell types as well, and are also upregulated after injury. We also found that, expressing Nfe2l3 in injured RGCs through localized intralocular viral vector delivery promotes neuroprotection and long-distance axon regeneration after optic nerve injury in vivo. Moreover, Nfe2l3 treatment provided a similar extent of neuroprotection and axon regeneration as viral vector-targeting of Pten and Klf9, which are prominent regulators of neuroprotection and long-distance axon regeneration. Finally, we bioinformatically characterized a gene network associated with Nfe2l3 in neurons, which revealed the association of Nfe2l3 with established mechanisms of neuroprotection and axon regeneration. Thus, Nfe2l3 is a novel neuroprotection and axon regeneration-promoting factor with a therapeutic potential for treating CNS injury and disease.

2024-02-22 | GSE253839 | GEO

Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo [bulkRNA-seq]

2024-02-22 | GSE253838 | GEO

Developmental and Injury-induced Changes in DNA Methylation in Regenerative versus Non-regenerative Regions of the Vertebrate (Xenopus laevis) Central Nervous System Characterized by Whole Genome Bisulfite Sequencing (WGBS)

Project description:Xenopus is uniquely suited for identifying core features of successful CNS axon regeneration, because parts of its CNS (e.g., eye), regenerate axons throughout life, whereas others (e.g., hindbrain) do so only as tadpoles. We performed bisulfite whole genome bisulfite methylation sequencing (WGBS) on juvenile frog eye after optic nerve injury, and on hindbrain samples from tadpole and juvenile frog after spinal cord injury during the peak phase of axon regeneration, to compare tissue-related and injury-induced differences in DNA methylation among them.

2022-01-05 | GSE183355 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq II)

Project description:Current treatments for neurodegenerative diseases and neural injuries fall short of success. One primary reason is that neurons in the mammalian central nervous system (CNS) lose their regeneration ability as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulation of mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons to support spontaneous axon regeneration following peripheral nerve injury. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 supported axon regeneration by systematically silencing the transcription of genes regulating synaptic function and inhibiting axon regeneration, while simultaneously activating various axon regeneration promoting factors. In particular, our study demonstrated that the GABA transporter 2 encoded by the gene Slc6a13 acted downstream of Ezh2 to control axon regeneration. Our study suggested that modulating chromatin accessibility was a promising strategy to promote CNS axon regeneration.

2023-12-22 | GSE247318 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq I)

2023-12-22 | GSE247317 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (ATAC-Seq)

2023-12-22 | GSE247315 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RRBS)

2023-12-22 | GSE247319 | GEO

Developmental and Injury-induced Changes in DNA Methylation in Regenerative versus Non-regenerative Regions of the Vertebrate (Xenopus laevis) Central Nervous System assayed by 5hmC MeDIP and by ChIP-seq for Histone Markers

Project description:Xenopus is uniquely suited for identifying core features of successful CNS axon regeneration, because parts of its CNS (e.g., eye), regenerate axons throughout life, whereas others (e.g., hindbrain) do so only as tadpoles. To aid in the interpretation of bisulfite whole genome methylation sequencing (WGBS) on juvenile frog eye after optic nerve injury, and on hindbrain samples from tadpole and juvenile frog after spinal cord injury during the peak phase of axon regeneration, we performed ChIP-seq for histone modifications associated with active gene expression (H3K4me3 & H3K27ac) and repressed gene expression (H3K27me3 & H3K9me3) on these same tissues, as well as DNA-immunoprecipitation sequencing (DIP seq) for 5-hydroxymethyl cytosine (5hmC) on eye samples during optic nerve regeneration.

2022-01-05 | GSE183350 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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