Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Leptin signalling promotes axonal regeneration in the peripheral and central nervous system [LepvGFP RNA-seq]

ABSTRACT: Axonal growth is limited or absent following peripheral or central nervous system injury respectively, inhibiting repair. The identification of novel growth-promoting molecular mechanisms is therefore a priority. In the search for dietary-dependent mechanisms that control neuronal regenerative ability, we found, via RNA sequencing, that growth-promoting intermittent fasting (IF) induced leptin expression in sensory neurons of the dorsal root ganglia (DRG). Surprisingly, leptin signalling, whose canonical function is to control energy homeostasis, was critical for the IF-dependent regenerative phenotype. In fact, neuronal conditional deletion of the leptin receptor significantly impaired the regenerative response elicited by IF. Overexpression of leptin in vivo in DRG neurons enhanced axonal regeneration following peripheral sciatic nerve crush (SNC) and central spinal cord injury. Lastly, RNA sequencing following leptin overexpression in DRG neurons showed a significant increase in regenerative gene expression and transcription after SCI, indicating a role for leptin in inducing a euchromatic, transcriptionally active environment that facilitates nervous system repair after injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE224220 | GEO | 2025/08/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Leptin signalling promotes axonal regeneration in the peripheral and central nervous system [IFvAL RNA-seq]

Project description:Axonal growth is limited or absent following peripheral or central nervous system injury respectively, inhibiting repair. The identification of novel growth-promoting molecular mechanisms is therefore a priority. In the search for dietary-dependent mechanisms that control neuronal regenerative ability, we found, via RNA sequencing, that growth-promoting intermittent fasting (IF) induced leptin expression in sensory neurons of the dorsal root ganglia (DRG). Surprisingly, leptin signalling, whose canonical function is to control energy homeostasis, was critical for the IF-dependent regenerative phenotype. In fact, neuronal conditional deletion of the leptin receptor significantly impaired the regenerative response elicited by IF. Overexpression of leptin in vivo in DRG neurons enhanced axonal regeneration following peripheral sciatic nerve crush (SNC) and central spinal cord injury. Lastly, RNA sequencing following leptin overexpression in DRG neurons showed a significant increase in regenerative gene expression and transcription after SCI, indicating a role for leptin in inducing a euchromatic, transcriptionally active environment that facilitates nervous system repair after injury.

2025-08-13 | GSE224284 | 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

Deregulation of neuronal polarization promotes axonal growth after spinal cord injury (ATAC-Seq)

Project description:The developmental maturation of a neuron requires the completion of neuronal polarization preceding the formation of a synapse. Whether neuronal polarization marks the decline in growth competence in the injured mammalian adult nervous system remains elusive. Here we show that gene expression and epigenetic signatures associated with the regenerative growth ability of dorsal root ganglia (DRG) sensory neurons are lost during the transition from a non-polarized to a polarized state. The transcriptional co-factor Cited2 was found to be epigenetically upregulated in immature DRG and following a regenerative injury, but it remained unchanged by a non-regenerative spinal cord injury (SCI). Next, Cited2 was overexpressed in DRG neurons in a model of SCI in mice where it promoted sensory axon growth and reversed the gene expression signatures associated with neuronal maturation. Importantly, Cited2 expression stirred the maturation of DRG neurons towards a non-polarized state. Together, these data suggest that the transition from a non-polarized to a polarized state marks the reversible loss of the regenerative ability of a neuron, thus paving the way to targeted repair strategies relying on neuronal de-maturation.

2024-01-01 | GSE224110 | GEO

Deregulation of neuronal polarization promotes axonal growth after spinal cord injury

2024-01-01 | GSE214722 | 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

scRNAseq analysis of mouse L4 whole dorsal root ganglions following sciatic nerve cush, dorsal root crush and spinal cord injury

Project description:After an injury in the adult mammalian central nervous system, lesioned axons fail to regenerate. This failure to regenerate contrasts with the remarkable potential of axons to grow following an injury in the peripheral nervous system. Peripheral sensory neurons with cell soma in dorsal root ganglia (DRG) switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Decades of research have focused on the signaling pathways elicited by injury in sensory neurons and in Schwann cells that insulate axons as central mechanisms regulating nerve repair. However, neuronal microenvironment is far more complex and is composed of multiple cell types including endothelial, immune and glial cells. Whether the microenvironment surrounding neuronal soma contribute to the poor regenerative outcomes following central injuries remains largely unexplored. To answer this question, we performed a single cell transcriptional profiling of the DRG neuronal microenvironment response to peripheral and central injuries. In dissecting the roles of the microenvironment contribution, we have focused on a poorly studied glia population of Satellite Glial Cells (SGC) surrounding the neuronal cell soma. Upon a peripheral injury, SGC contribute to axon regeneration via Fatty acid synthase (Fasn)-PPARα signaling pathway. Our analysis reveals that in response to central injuries, SGC do not activate the PPAR signaling pathway. However, induction of this pathway with fenofibrate, an FDA- approved PPARα agonist used for dyslipidemia treatment, rescued axon regeneration following an injury to the central nerves. Collectively, our results uncovered a previously unappreciated role of the neuronal microenvironment differential response in central and peripheral injuries.

2021-09-12 | GSE158892 | GEO

Robust axonal regeneration occurs in the injured CAST/Ei mouse central nervous system

Project description:Axon regeneration in the central nervous system (CNS) requires reactivating injured neurons’ intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater spouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. These screens are presented here. Biological quadruplicate - Mouse tissue - Naïve Dorsal Root Ganglia (DRG) and 5 day post sciatic nerve crush DRG - x9 strains.

2015-07-22 | E-GEOD-67130 | biostudies-arrayexpress

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

2015-05-14 | GSE55424 | GEO

Comprehensive mapping of 5-hmC epigenetic dynamics in axon regeneration

Project description: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.

2016-12-09 | GSE85972 | 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