Decellularized Spinal Cord Matrix Manipulate Glial Niche Alteration via Serglycin Mediated Signalling Pathway [scRNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus Homo sapiens
PROVIDER: GSE202731 | GEO | 2022/12/31
REPOSITORIES: GEO
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Project description:Neonatal spinal cord tissues exhibit remarkable regenerative capabilities than adult 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 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 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 than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in rats with spinal cord injury (SCI). It suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.
2024-03-01 | GSE255188 | GEO
Project description:Transected spinal cord injury (SCI) results in significant structural disruption of the spinal cord. The reconstruction of neural pathways following SCI faces several key challenges, including inadequate endogenous neural stem cells (NSCs) and poor neurogenesis in natural repair process, and concerns related to the long-term survival of neurons following exogenous transplantation. In the current study, we report an oligonucleotide aptamer drug (Apt19S) which is first proven to recruit endogenous NSCs to the site of injury following SCI, and therefore develop a bionic spinal cord scaffold that can sustainedly release Apt19S and neurotrophin-3 (NT-3) to provide the neurogenic niche with the necessary mechanical properties and support for in situ spinal cord repair. The bionic scaffold successfully recruited a significant number of endogenous NSCs in vivo and established a neurogenic niche that was abundant in NT-3, thereby promoting neuronal differentiation and the formation of neuronal networks Regenerated nerve fibers including 5-hydroxytryptamine-positive nerve fibers and corticospinal tract grew robustly into the injury site and generated synaptic connections with the newborn neurons. Collectively, our findings indicate that our aptamer-based bionic spinal cord scaffold elicits a robust neurogenesis process in situ, breaking the limitations imposed by poor self-repair ability in the adult spinal cord.
2023-10-19 | GSE245409 | GEO
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.
2024-03-01 | GSE242908 | GEO
Project description:Neonatal spinal cord tissues exhibit remarkable regenerative capabilities than adult 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 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 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 than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in rats with spinal cord injury (SCI). It suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.
2024-01-29 | PXD048991 | iProX
Project description:Recent studies in brain and spinal cord have revealed the heterogenous nature of astrocytes; however, how diverse constituents of astrocyte lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We performed single-cell RNA-sequencing (scRNA-seq) of astrocyte lineage cells from sub-chronic spinal cord injury (SCI) models, identified and compared with the subpopulations in the acute stage data. We found the subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Our analyses revealed the molecular signature, location and morphologies of potential residential neural progenitors or neural stem cells in the adult spinal cord before and after injury, and the intermediate cells enriched in neuronal markers that could potentially transition into other subpopulations. The investigation of stage-specific cell-cell communications among astrocyte lineage cells and with other cell types in the tissue generated valuable insight into signaling pathway networks in SCI. This study has significantly expanded the knowledge of the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.
2023-09-27 | GSE202627 | GEO
Project description:Spinal cord injury (SCI) represents a major debilitating health issue with a direct socioeconomic burden on the public and private sectors worldwide. Although several studies have been conducted to identify the molecular progression of injury sequel due from the lesion site, still the exact underlying mechanisms and pathways of injury development have not been fully elucidated. In this work, based on OMICs, 3D MALDI imaging, cytokines arrays, confocal imaging we established for the first time that molecular and cellular processes occurring after spinal cord injury (SCI) are altered between the lesion proximity, i.e., rostral and caudal segments nearby the lesion (R1-C1) whereas segments distant from R1-C1, i.e., R2-C2 and R3-C3 levels co-expressed factors implicated in neurogenesis. Delay in T regulators recruitment between R1 and C1 favor discrepancies between the two segments. This is also reinforced by presence of neurites outgrowth inhibitors in C1, absent in R1. Moreover, the presence of immunoglobulins (IgGs) in neurons at the lesion site at 3 days, validated by mass spectrometry, may present additional factor that contributes to limited regeneration. Treatment in vivo with anti-CD20 one hour after SCI did not improve locomotor function and IgG expression. These results open the door of a novel view of the SCI treatment by considering the C1 as the therapeutic target.
2016-06-08 | PXD003375 | Pride
Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Analysis of the areas directly (spinal cord) and indirectly (raphe and sensorimotor cortex) affected by injury will help understanding mechanisms of SCI. Hypothesis: Areas of the brain primarily affected by spinal cord injury are the Raphe and the Sensorimotor cortex thus gene expression profiling these two areas might contribute understanding the mechanisms of spinal cord injury. Specific Aim: The project aims at finding significantly altered genes in the Raphe and Sensorimotor cortex following an induced moderate spinal cord injury in T9.
2007-10-08 | E-GEOD-2270 | biostudies-arrayexpress
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:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Hypothesis: Spinal cord injury (SCI) induces a cascade of molecular events including the activation of genes associated with transcription factors, inflammation, oxidative stress, ionic imbalance, apoptosis and neuroregeneration which suggests the existance of endogenous reparative attempts. However, not all mechanisms following SCI are well known. Specific Aim: The goal of this project is to analyze the molecular events following spinal cord injury 1 cm above, below, and at the site of injury (T9), aiming at finding potential new targets to improve recovery and therapy.
2007-09-04 | E-GEOD-464 | biostudies-arrayexpress
Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Analysis of the areas directly (spinal cord) and indirectly (raphe and sensorimotor cortex) affected by injury will help understanding mechanisms of SCI. Hypothesis: Areas of the brain primarily affected by spinal cord injury are the Raphe and the Sensorimotor cortex thus gene expression profiling these two areas might contribute understanding the mechanisms of spinal cord injury. Specific Aim: The project aims at finding significantly altered genes in the Raphe and Sensorimotor cortex following an induced moderate spinal cord injury in T9. Keywords: other
2005-02-11 | GSE2270 | GEO