Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA279017 | ENA |
REPOSITORIES: ENA
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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
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.
2015-07-22 | GSE67130 | GEO
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
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.
2015-05-14 | GSE55424 | GEO
Project description:Peripheral nerve regeneration after injury is a complex process involving a large number of transcriptional changes. How these changes impact the regenerative outcome is though, poorly understood. Here, we take advantage of the genetically based differences in the peripheral and central regenerative capacity of CAST/Ei and C57BL/6j inbred mice to better understand the molecular bases driving superior regeneration in the CAST/Ei mouse strain.
2017-08-01 | GSE98416 | GEO
Project description:Peripheral nerve regeneration after injury is a complex process involving a large number of transcriptional changes. How these changes impact the regenerative outcome is though, poorly understood. Here, we take advantage of the genetically based differences in the peripheral and central regenerative capacity of CAST/Ei and C57BL/6j inbred mice to better understand the molecular bases driving superior regeneration in the CAST/Ei mouse strain. Single cell RNA sequencing highlighted the existence of three populations of cells, one of which expressed genes enriched for mature neuronal function, another one had a gene expression profile enriched for an immature dedifferentiated state while the third one showed an intermediate profile between these two extremes. The immature expression state was observed after injury in both strains but a larger proportion of the CAST/Ei neurons retained an expression pattern consistent with neuronal identity whereas a larger proportion of C57BL/6 neurons acquired an immature gene expression state accompanied by expression of stress markers. This finding suggests that unexpectedly, maintenance of a mature differentiated state in injured neurons increased regenerative success.
2017-08-01 | GSE98415 | GEO
Project description:Purpose: A) compare the response to an axonal injury in the peripheral vs central nervous system B) clarify the role of HDAC3 in axonal regeneration Results: we found that after peripheral axonal injury there is a higher number of differentially expressed genes regulated by HDAC3 with respect to central injury with a number of genes associated with regenerative pathways
2018-10-01 | GSE104977 | GEO
Project description:Purpose: A) compare the response to an axonal injury in the peripheral vs central nervous system B) clarify the mechanism of Reactive Oxygen Species-dependent axonal regeneration Results: we found that after peripheral axonal injury there is a higher number of differentially expressed genes with respect to central injury. Moreover,inflammation related genes and regeneration-associated genes were differentially regulated after peripheral injury and H2O2, but less after central injury. Signalling pathways and biological processes related to injury-dependent nerve regeneration were reduced with the addition of NAC at the time of sciatic injury compared to vehicle.
2018-07-06 | GSE97090 | GEO
Project description:Among the vertebrates, teleost and urodele amphibians are capable of regenerating their central nervous system. We have used crush injury method on zebrafish spinal cord, which is a common mammalian mode of injury in spinal cord. To identify the molecular mechanisms of the underlying cellular events during regeneration of zebrafish spinal cord, we have employed high density oligonucleotide microarrays and profiled the temporal transcriptome dynamics during the entire phenomenon. A total of 3842 genes expressed differentially with significant fold changes during spinal cord regeneration. Cluster analysis revealed event specific dynamic expression of genes related to inflammation, cell death, cell migration, cell proliferation, neurogenesis, neural patterning and axonal regrowth. We have also validated the expression pattern of 14 genes (which include inflammatory regulators, cell cycle regulators, pattern forming genes and signaling molecules) by different methodologies. Spatio-temporal analysis of STAT3 expression suggested its possible function in controlling inflammation and cell proliferation. Genes involved in the proliferating neural progenitors and their dorso-ventral patterning (sox2 and dbx2) are differentially expressed. Injury induced cell proliferation is controlled by many cell cycle regulators and some of them also show their common expression in other regenerating systems like fin, heart and retina. We also reported unusual expression pattern of certain pathway genes like one carbon folate metabolism and N-glycan biosynthesis which have not been reported during regeneration of spinal cord. Genes like stat3, socs3, atf3, mmp9 and sox11, which are known to control peripheral nervous system (PNS) regeneration in mammals, are also upregulated in zebrafish spinal cord injury (SCI) thus creating PNS like environment after injury. Our study provides a comprehensive genetic blue print of diverse cellular response(s) during regeneration of zebrafish spinal cord that could be used to induce successful regeneration in mammals. The spinal cord has been injured by crushing dorso-ventrally for 1 sec with a number 5 Dumont forceps at the level of 15th/16th vertebrae. Later the wound were sealed by placing a suture. Both spinal cord injured and sham operated fish were allowed to regenerate and the progress of regeneration was observed after 1, 3, 7, 10 and 15 days of injury. Zebrafishes were anesthetized deeply for 5 minutes in 0.1% tricaine (MS222; Sigma, USA) and approximately 1mm length of spinal cord both rostrally and caudally from injury epicenter were dissected out from 50-60 fishes in each batch and pooled for RNA extraction.
2012-12-01 | E-GEOD-39295 | biostudies-arrayexpress
Project description:Regeneration occurs in the CNS of CAST/Ei mice as a consequence of enhanced Activin signaling
| PRJNA239562 | ENA