Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comprehensive mapping of 5-hmC epigenetic dynamics in axon regeneration

ABSTRACT: In contrast to CNS neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated, along with increased 5-hydroxymethylcytosine (5-hmC) in DRG neurons. We generated genome-wide 5-hmC maps in adult DRG, which demonstrated that peripheral and central axotomy (no regenerative effect) triggered differential 5-hmC changes that are associated with distinct signaling pathways. 5-hmC was altered in half of regeneration-associated genes (RAGs), supporting its role for RAG regulation. Our analyses predicted transcription factors HIF-1, STAT and IRF that may collaborate with Tet3 for 5-hmC modifications. Intriguingly, central axotomy lead to widespread 5-hmC modifications with little overlap with peripheral axotomy, thus potentially constituting a roadblock for regeneration. Our study revealed 5-hmC as a previously unrecognized epigenetic mechanism underlying the divergent responses after axonal injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE85972 | GEO | 2016/12/09

SECONDARY ACCESSION(S): PRJNA339858

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Circadian clock regulator Bmal1 gates axon regeneration via Tet3-5hmC mediated epigenetics

Project description:Axon regeneration of dorsal root ganglia (DRG) neurons after peripheral axotomy involves epigenetic reconfigurations that rewire gene regulatory circuits to establish regenerative gene program. However, the mechanisms and transcriptional regulators remain poorly understood. Here, we conducted an unbiased survey of DNA differentially hydroxymethylated regions (DhMRs) in DRG after peripheral lesion, which identified enriched binding motif for Bmal1, a transcription factor and a central regulator of the circadian clock. Through applying conditional deletion of Bmal1, in vitro and in vivo models of axon regrowth, and transcriptomic profiling, we showed that Bmal1 inhibits axon regeneration in part through Tet3-dependent manner. Mechanistically, Bmal1 functions as a gatekeeper of neuroepigenetic injury responses by limiting Tet3 expression and restricting 5hmC modifications. Notably, Bmal1-regulated genes after axotomy not only concern axon guidance and axon regrowth, but also stress responses, energy homeostasis, and neuroinflammation. Furthermore, we uncovered diurnal oscillation of Tet3 and 5hmC in DRG neurons, and this epigenetic rhythm corresponded to time-of-day effect on axon growth potential. Collectively, our studies showed that Bmal1 deletion mimics the conditioning lesion in lifting epigenetic barriers to enhance axon regeneration.

2023-08-02 | GSE233367 | GEO

RNA-Seq of regenerating DRG neurons

Project description:To identify isoform differential expression underlying peripheral nerve regeneration we performed RNA-Sequencing on DRG neurons after axotomy.

2017-07-12 | GSE59547 | GEO

The Peripheral Atf3+ Neuronal Population is Responsible for Nerve Regeneration at Early Stage of Nerve Injury Revealed by Single-Cell RNA Sequencing

Project description:Peripheral nerve injury (PNI) could transform primary somatosensory neurons into regenerative state. However, details of transcriptomic changes associated to nerve regeneration of somatosensory neurons maintain unclear. 10x single-cell RNA sequencing (scRNA-seq) was conducted on mice dorsal root ganglia (DRG) cells after early stage of nerve injury on day 3 post-constriction chronic injury (CCI). We observed that a novel CCI-induced neuronal population (CIP) emerged and expressed high levels of activating transcription factor (Atf3), a neuronal injury marker. CIP neurons highly expressed regenerative associated genes (RAGs) and were enriched in regeneration-related gene ontology (GO) terms, suggesting these neurons could be a pro-regenerative population. Moreover, intercellular communication networks showed that CIP neurons have a close communication to satellite glia cells (SGCs) and specifically transmitted strong Fgf3-Fgfr1 signaling to SGCs, which could initiate regeneration-associated transcriptional changes of SGCs. This study also confirmed that the regenerative progress occurred at the early stage of nerve injury because immunohistochemistry showed the expression of ATF3 significantly increased since day 3 post-CCI and decreased at 1 month. Our bioinformatics analysis at single-cell resolution advances the knowledge of regenerative dynamic transcriptional changes of DRG cells after injuries and their underlying molecular mechanisms.

2024-02-09 | GSE255014 | GEO

Jun promotes axon regeneration by binding enhancer sites and dimerizing with Atf3

Project description:Axon regeneration is a necessary step toward functional recovery after spinal cord injury. The AP-1 transcription factor c-Jun has long been known to play an important role in directing the transcriptional response of Dorsal Root Ganglion (DRG) neurons to peripheral axotomy that results in successful axon regeneration. Here we performed ChIPseq for Jun in mouse DRG neurons after a sciatic nerve crush or sham surgery in order to measure the changes in Jun’s DNA binding in response to peripheral axotomy. We found that the majority of Jun’s injury-responsive changes in DNA binding occur at putative enhancer elements, rather than proximal to transcription start sites. We also used a series of single polypeptide chain tandem transcription factors to test the effects of different Jun-containing dimers on neurite outgrowth in cortical and hippocampal neurons. These experiments demonstrated that dimers composed of Jun and Atf3 promoted neurite outgrowth in rat CNS neurons. Our work provides new insight into the mechanisms underlying Jun’s role in axon regeneration.

2018-08-06 | GSE105442 | GEO

MeDIP-chip from dorsal root ganglia (DRG) tissue from wildtype mice, for 5-methyl-cytosine

Project description:Nerve injury in the peripheral nervous system allows spontaneous regeneration, in contrast to injury of central nerves, which lead to a differential expression pattern of regeneration-associated genes and others. These genes might be regulated by promoter DNA methylation As regeneration model, DRG tissue was analyzed for methyated gene promoters and CpG islands following both injury types. A differential methylation pattern could be identified, although most genes remained unmethylated. comparison of DRG following either sciatic nerve axotomy (SNA) or dorsal column axotomy (DCA) - each 'real injury or sham' - at 1, 3 or 7 days post-injury vs. 'naive', Each sample was pooled from two mice, yielding an immunoprecipitated sample ('Test') and an input genomic DNA sample (Ref). altogether 33 microarrays were used for 13 conditions with triplicate arrays for 'real injury' or 'naive' samples, and duplicate arrays for 'sham' samples.

2014-03-05 | E-GEOD-55514 | biostudies-arrayexpress

Major differences in transcriptional alterations in dorsal root ganglia between spinal cord injury and peripheral neuropathic pain models

Project description:Chronic, often intractable pain is caused by neuropathic conditions such as peripheral nerve injury (PNI) and spinal cord injury (SCI). These conditions are associated with alterations in gene and protein expression correlated with functional changes in somatosensory neurons having cell bodies in dorsal root ganglia (DRGs). Most studies of DRG transcriptional alterations have utilized PNI models where axotomy-induced changes important for regeneration may overshadow changes that drive neuropathic pain. Both PNI and SCI produce DRG neuron hyperexcitability linked to pain, but contusive SCI produces little peripheral axotomy or peripheral nerve inflammation. Thus, comparison of transcriptional signatures of DRGs across PNI and SCI models may highlight pain-associated transcriptional alterations that don’t depend on peripheral axotomy and associated effects such as peripheral Wallerian degeneration. Data from our rat thoracic SCI experiments were combined with meta-analysis of whole-DRG RNA-seq datasets from prominent rat PNI models. Striking differences were found between transcriptional responses to PNI and SCI, especially in regeneration-associated genes and long noncoding RNAs. Many transcriptomic changes after SCI were also found after corresponding sham surgery, indicating they were caused by injury to surrounding tissue rather than to the spinal cord itself. Another unexpected finding was of few transcriptomic similarities between any rat neuropathic pain model and the only reported transcriptional analysis of human DRGs linked to neuropathic pain. These findings show that DRGs exhibit complex transcriptional responses to central and peripheral neural and tissue injury. Although few genes in DRG cells show similar changes in gene expression across all these painful conditions, the few widely shared transcriptional alterations promise novel insights into fundamental mechanisms within DRGs that can drive neuropathic pain.

2022-10-20 | GSE202111 | GEO

The circadian clock time tunes axonal regeneration

Project description:Peripheral nervous system injuries lead to long-term neurological disability due to limited axonal regenerative ability. Injury-dependent and more recently injury-independent physiological mechanisms have provided important molecular insight into regenerative mechanisms. However, whether common molecular denominators underpinning both injury-dependent and independent biological processes exist remains unclear. We initially performed a comparative analysis of recently generated transcriptomic datasets associated with the regenerative ability of sciatic dorsal root ganglia (DRG). Surprisingly, circadian rhythms were identified as a the most significantly enriched biological process associated with regenerative capability. We demonstrate that DRG neurons possess an endogenous circadian clock with a 24h oscillations of circadian genes and that their regenerative ability displays a diurnal oscillation in a mouse model of sciatic nerve injury. Consistently, transcriptomic analysis of DRG neurons showed a significant time-of-day dependent enrichment for processes associated with neuronal development and axonal growth, for regeneration and circadian associated genes, including the core clock genes Bmal1 and Clock. Indeed, DRG-specific ablation of the non-redundant clock gene Bmal1showed that it is required for regenerative gene expression, neuronal intrinsic circadian axonal regeneration and target reinnervation. Lastly, Lithium, a chrono-active compound, enhanced nerve regeneration, in wildtype but not in clock genes Bmal1 and Cry1/2-deficient mice. Together, these data demonstrate that daily rhythms and the circadian clock fine-tune the regenerative response of DRG neurons, and they advocate for the use of chrono-active strategies in time-day dependent modulation of nerve repair.

2024-01-19 | GSE235687 | GEO

RNA-sequencing of injured cultured dorsal root ganglion neurons over time

Project description:Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons in vivo and that all neuronal subtypes are represented. This eDRG neuronal culture does not contain other non-neuronal cell types. Next, we performed RNA sequencing at different time points after in vitro axotomy. Analysis of differentially expressed genes revealed upregulation of know regeneration associated transcription factors, including Jun Atf3 and Rest, paralleling the axon injury response in vivo. Analysis of transcription factor binding sites in differentially expressed genes revealed other known transcription factors promoting axon regeneration, such as Myc, Hif1a, Pparg, Ascl1a, Srf, as well as other transcription factors not yet characterized in axon regeneration. We next tested if overexpression of known and novel candidate transcription factors alone or in combination promote axon regeneration in vitro. Our results demonstrate that expression of Ctcf with Yy1 or E2f2 enhances in vitro axon regeneration. Our analysis reveals that pairs of transcription factors can functionally synergize to promote axon regeneration and highlight that transcription factor interaction play an important role as a regulator of axon regeneration.

2022-06-20 | GSE138480 | GEO

H3K9ac, H3K27ac, H3K27me3 ChIP sequencing and ATAC sequencing of L4-L6 Dorsal Root Ganglia upon spinal or sciatic axonal injury

Project description:Purpose: compare the epigenetic response of DRG neurons to an axonal injury in the peripheral vs central nervous system by measuring accessible chromatin and several histone marks Results: we found that after peripheral axonal injury there is a much greater number of epigenetic changes than after central spinal injury, and that these epigenetic changes after peripheral axotomy tended toward increased chromatin accessibility.

2019-06-19 | GSE108806 | GEO

Regeneration occurs in the CNS of CAST/Ei mice as a consequence of enhanced Activin signaling

Project description:We screened nine genetically diverse inbred mouse strains for differences in axonal growth of adult dorsal root ganglion (DRG) neurons on CNS myelin. Naïve DRG neurite outgrowth on myelin was very limited, but preconditioning the neurons by a prior sciatic nerve crush increased axonal growth substantially across all strains, with by far the greatest change in neurons from CAST/Ei mice. Three independent in vivo CNS injury models revealed greater capacity for CNS axonal regeneration in CAST/Ei than C57BL/6 mice. Full-genome expression profiling of naïve and pre-conditioned DRGs across all strains revealed Activin-βA (Inhba) as the transcript whose expression most closely correlated with axonal growth on myelin. In vitro and in vivo gain- and loss-of-function experiments confirmed that Activin promotes axonal growth in the CNS. Substantial regeneration is possible, therefore, in the injured mammalian CNS when Activin signaling is intrinsically high, as in CAST/Ei or when extrinsically modulated in other strains. 9 strains, 4 replicates per strain, 2 conditions (naïve and axotomy) = 72 samples. 2 samples were excluded because technical outliers (AJ_AX5D_1 and AJ_NAIVE_4 excluded from the normalized data but included in the raw data)

2015-05-14 | E-GEOD-55424 | biostudies-arrayexpress

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