Regulation of stem cell identity by miR-200a during spinal cord regeneration
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ABSTRACT:
PROVIDER: PRJNA803256 | ENA |
REPOSITORIES: ENA
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Project description:Salamanders have the remarkable ability to functionally regenerate after spinal cord transection. In response to injury, GFAP+ glial cells in the axolotl spinal cord proliferate and migrate to replace the missing neural tube and create a permissive environment for axon regeneration. In this paper we show that miR-200a acts to repress expression of Brachyury in sox2 positive progenitor cells in the axoltol spinal cord after spinal cord injury but after tail amputation when multiple tissue types must be regenerated then mir-200a is downregualted allowing progenitor cells in the spinal cord to naturally become bipotent progenitors which can give rise to muscle and neural cell types. When miR-200a is inhibited after spinal cord injury then these cells also express BRachyury cna can form muscle.
2022-02-10 | GSE196098 | GEO
Project description:Salamanders have the remarkable ability to functionally regenerate after spinal cord transection. In response to injury, GFAP+ glial cells in the axolotl spinal cord proliferate and migrate to replace the missing neural tube and create a permissive environment for axon regeneration. Molecular pathways that regulate the pro-regenerative axolotl glial cell response are poorly understood. Here we show axolotl glial cells up-regulate AP-1cFos/JunB after injury, which promotes a pro-regenerative glial cell response. Axolotl glial cells directly repress c-Jun expression via up-regulation of miR-200a. Inhibition of miR-200a during regeneration causes defects in axonal regrowth and transcriptomic analysis revealed that miR-200a inhibition leads to differential regulation of genes involved with reactive gliosis, the glial scar, ECM remodeling and axon guidance. This work identifies a novel role for miR-200a in inhibiting reactive gliosis in glial cell in axolotl during spinal cord regeneration
2019-03-19 | GSE122939 | GEO
Project description:Label-free mass spectrometry-based quantitative proteomics was applied to a larval zebrafish spinal cord injury model, which allows axon regeneration and functional recovery within two days (days post lesion; dpl) after a spinal cord transection in 3 day-old larvae (dpf). Proteomic profiling of the lesion site was performed at 1 dpl and 2 dpl as well as corresponding age-matched unlesioned control tissue (4 dpf as control for 1 dpl; 5 dpf as control for 2 dpl).
2023-09-06 | PXD037590 | Pride
Project description:Label-free mass spectrometry-based quantitative proteomics was applied to a larval zebrafish spinal cord injury model, which allows axon regeneration and functional recovery within two days (days post lesion; dpl) after a spinal cord transection in 3 day-old larvae (dpf). Proteomic profiling was performed of the lesion site at 1 dpl in control animals and animals with pdgfrb+ cell-specific overexpression of either zebrafish chondoradherin (chad; chad-mCherry fusion), fibromodulin a (fmoda; fmoda-mCherry fusion), lumican (lum; lum-mCherry fusion) or prolargin (prelp; prelp-mCherry fusion).
2023-09-06 | PXD037605 | Pride
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:Spinal cord injury triggers a strong innate inflammatory response in both non-regenerative mammals and regenerative zebrafish. Neutrophils are the first immune population to be recruited to the injury site. Yet, their role in the repair process, particularly in a regenerative context, remains largely unknown. Here, we show that, promoting neutrophil inflammation resolution by inhibiting Cxcr4 boosts cellular and functional regeneration. Neutrophil-specific RNA-seq analysis reveals an enhanced activation state that correlates with a transient increase in tnf-a expression in macrophage/microglia populations. Conversely, blocking neutrophil recruitment through Cxcr1/2 inhibition diminishes the presence of macrophage/microglia at the injury site and impairs spinal cord regeneration. Altogether, these findings provide new insights into the role of neutrophils in spinal cord regeneration, emphasizing the significant impact of their immune profile on the outcome of the repair process.
2024-07-03 | GSE271113 | GEO
Project description:AP-1cFos/JunB/miR-200a regulate the pro-regenerative glial cell response during axolotl spinal cord regeneration
| PRJNA506973 | ENA
Project description:Neonatal spinal cord tissues exhibit remarkable regenerative capabilities compared to adult tissues following injury. Although some cellular signaling pathways involved in the process have been identified, the specific role of extracellular matrix (ECM) responsible for neonatal spinal cord regeneration has remained elusive. Here we revealed that early developmental spinal cord contained a higher abundance of ECM proteins associated with neural development and axon growth but fewer inhibitory proteoglycans compared to adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserve the major difference of native spinal cord tissues in both stages. Compared to DASCM, DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs), as well as facilitated the long-distance axonal outgrowth and axon regeneration of spinal cord organoids. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to the remarkable neural regeneration ability. Furthermore, DNSCM demonstrated superior performance when used as a delivery vehicle for NPCs and organoids in rats with spinal cord injury (SCI). It suggests that ECM cues derived from different development stage might contribute to the distinct regeneration ability of spinal cord.
2023-09-13 | PXD045337 | iProX
Project description:Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECMproteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) inDNSCMwere identified as contributors tothese abilities. Furthermore,DNSCMdemonstrated superior performance as a delivery vehicle forNPCs and organoids in spinal cord injury (SCI)models. This suggests that ECMcues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.
2024-03-01 | GSE242908 | 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.
2012-12-01 | GSE39295 | GEO