Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Upregulation of developmentally-downregulated miR-1247-5p promotes neuroprotection and axon regeneration in vivo [Small-RNA-seq]

ABSTRACT: Numerous micro-RNAs (miRNAs) affect neurodevelopment and neuroprotection, but potential roles of many miRNAs in regulating these processes are still unknown. Here, we used the retinal ganglion cell (RGC) central nervous system (CNS) projection neuron and optic nerve crush (ONC) injury model, to optimize a mature miRNA arm-specific quantification method for characterizing the developmental regulation of miR-1247-5p in RGCs, investigated whether injury affects its expression, and tested whether upregulating miR-1247-5p-mimic in RGCs promotes neuroprotection and axon regeneration. We found that, miR-1247-5p is developmentally-downregulated in RGCs, and is also further downregulated after ONC. Importantly, RGC-specific upregulation of miR-1247-5p promoted neuroprotection and axon regeneration after injury in vivo. To gain insight into the underlying mechanisms, we analyzed by bulk-mRNA-seq embryonic and adult RGCs, along with adult RGCs transduced by miR-1247-5p-expressing viral vector, and identified developmentally-regulated cilial and mitochondrial biological processes, which were reinstated to their embryonic levels in adult RGCs by upregulation of miR-1247-5p. Because axon growth is also a developmentally-regulated process, in which mitochondrial dynamics play important roles, it is possible that miR-1247-5p promoted neuroprotection and axon regeneration through regulating mitochondrial functions.

ORGANISM(S): Mus musculus

PROVIDER: GSE252516 | GEO | 2024/01/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Upregulation of developmentally-downregulated miR-1247-5p promotes neuroprotection and axon regeneration in vivo [RNA-seq]

Project description:Numerous micro-RNAs (miRNAs) affect neurodevelopment and neuroprotection, but potential roles of many miRNAs in regulating these processes are still unknown. Here, we used the retinal ganglion cell (RGC) central nervous system (CNS) projection neuron and optic nerve crush (ONC) injury model, to optimize a mature miRNA arm-specific quantification method for characterizing the developmental regulation of miR-1247-5p in RGCs, investigated whether injury affects its expression, and tested whether upregulating miR-1247-5p-mimic in RGCs promotes neuroprotection and axon regeneration. We found that, miR-1247-5p is developmentally-downregulated in RGCs, and is also further downregulated after ONC. Importantly, RGC-specific upregulation of miR-1247-5p promoted neuroprotection and axon regeneration after injury in vivo. To gain insight into the underlying mechanisms, we analyzed by bulk-mRNA-seq embryonic and adult RGCs, along with adult RGCs transduced by miR-1247-5p-expressing viral vector, and identified developmentally-regulated cilial and mitochondrial biological processes, which were reinstated to their embryonic levels in adult RGCs by upregulation of miR-1247-5p. Because axon growth is also a developmentally-regulated process, in which mitochondrial dynamics play important roles, it is possible that miR-1247-5p promoted neuroprotection and axon regeneration through regulating mitochondrial functions.

2024-01-26 | GSE252514 | GEO

Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells [2]

Project description:Neurons of the central nervous system (CNS) display only a limited ability to survive and regenerate their axons after an injury. In mice, 85% of retinal ganglion cells (RGCs) die within 2 weeks of axotomy by optic nerve crush (ONC) and only few survivors regenerate axons. In the past years, a multitude of interventions have been identified to improve RGC survival and regeneration after an injury, however, each only protects a subset of neurons and stimulates axon regrowth in an even smaller set.. Here, we sought out to elucidate the molecular mechanisms underlying this selective responsiveness and investigated genes regulated by three well established survival and regeneration-promoting interventions – activation of the MTOR pathway via deletion of its inhibitor Pten, activation of the Jak/Stat-pathway by deletion of its endogenous inhibitor Socs3, and overexpression of the neurotrophic cytokine CNTF. Analysis of the transcriptomes from >125,000 single RGCs at various time points after ONC showed that while broad survival of all RGC types could be induced with each intervention, type-independent axon regeneration was only overcome with the manipulation of multiple pathways. Those RGCs were able to mitigate the injury response and simultaneously upregulated survival and regeneration associated programs (prior and after injury). Four independent ways of analysis identified these programs to be differentially regulated among RGCs, with distinct signatures for degenerating, surviving and regenerating cells. Finally, testing some genes associated with the regeneration-program in vivo identified potential future therapeutic targets to promote neuroprotection and axonal regeneration.

2022-06-28 | GSE202154 | GEO

Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells [1]

2022-06-28 | GSE201254 | 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

Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury [third-party re-analysis]

Project description:Collapsin response mediator proteins (Crmps) play roles in neuronal development and axon growth. However, neuronal-specific roles of Crmp1, Crmp4, and Crmp5 in regeneration of injured central nervous system (CNS) axons in vivo are unclear. Here, we analyzed developmental and subtype-specific expression of Crmp genes in retinal ganglion cells (RGCs), tested whether overexpressing Crmp1, Crmp4, or Crmp5 in RGCs through localized intralocular AAV2 delivery promotes axon regeneration after optic nerve injury in vivo, and characterized developmental co-regulation of gene-concept networks associated with Crmps. We found that all Crmp genes are developmentally downregulated in RGCs during maturation. However, while Crmp1, Crmp2, and Crmp4 were expressed to a varying degree in most RGC subtypes, Crmp3 and Crmp5 were expressed only in a small subset of RGC subtypes. We then found that after optic nerve injury, Crmp1, Crmp4, and Crmp5 promote RGC axon regeneration to varying extents, with Crmp4 promoting the most axon regeneration and also localizing to axons. We also found that Crmp1 and Crmp4, but not Crmp5, promote RGC survival. Finally, we found that Crmp1, Crmp2, Crmp4, and Crmp5's ability to promote axon regeneration is associated with neurodevelopmental mechanisms, which control RGC’s intrinsic axon growth capacity.

2023-04-10 | GSE228486 | GEO

Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury [bulk RNA-seq]

2023-04-10 | GSE228485 | 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

Amacrine cells suppress retinal ganglion cells survival and optic nerve regeneration bu releasing intersynaptic zinc

Project description:Retinal ganglion cells (RGCs) convey the major output of information collected from the eye to the brain. RGCs are irreversibly lost when injured in degenerative diseases such as glaucoma; this failure can be partially reversed by eliminating the retinal mobile zinc (Zn2+) and leads to substantial axon regeneration. ZnT3 conditional knockout in retinal amacrine cells blocks the synaptic transport of Zn2+, which promotes RGC survival and axonal regeneration in optic nerve jinjury (ONC). Here, we conducted an mRNA sequencing of flow cytometry-isolated RGCs 3 days after optic nerve injury with or without ZnT3 expression in retinal amacrine cells.

2023-07-01 | GSE213937 | GEO

Sox11 expression in adult retina promotes regeneration of some ganglion cell types but kills others

Project description:At least 30 types of retinal ganglion cell (RGC) send distinct messages through the optic nerve to the brain. Strategies for promoting regeneration of RGC axons following injury act on only some of these types. Here we tested the hypothesis that over-expressing developmentally important transcription factors in adult RGCs could reprogram them to a “youthful” growth-competent state and promote regeneration of other types. From a screen of transcription factors expressed by developing RGCs, we found one, Sox11, that induced substantial axon regeneration. Transcriptome profiling confirmed that Sox11 activates genes involved in cytoskeletal remodeling and axon growth. Remarkably, alpha-RGCs, which preferentially regenerate following treatments such as PTEN deletion, were killed by Sox 11. Thus, Sox 11 promotes regeneration of non-alpha RGCs, which are refractory to PTEN. We conclude that Sox11 can reprogram adult RGCs to a growth-competent state and that different growth-promoting interventions act on distinct neuronal types.

2017-06-25 | GSE87046 | 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