Early life injury alters spinal astrocyte development
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PROVIDER: PRJNA1223400 | ENA |
REPOSITORIES: ENA
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Project description:Neonatal injury alters synaptic transmission and plasticity in the spinal superficial dorsal horn (SDH), resulting in aberrant amplification of ascending nociceptive transmission. Astrocytes orchestrate synapse development and function across the CNS and have been shown to play a critical role in the emergence and maintenance of persistent pain. However, very little is currently known about the postnatal development of spinal astrocytes, nor about how the maturation of SDH astrocytes is impacted by early life injury. Here, we used a hindpaw incision model of postsurgical pain in postnatal day (P) 3 mice to elucidate the effects of neonatal injury on the maturation of SDH astrocytes. Three-dimensional morphological analysis of individual astrocytes revealed that incision elicits age-dependent changes to astrocyte structure. At P4, spinal astrocytes in incised mice show increased size and complexity compared to naïve controls. This is reversed at P10 and P24, as astrocytes from incised mice are smaller and less ramified compared to their naïve counterparts. Transcriptomic analysis of spinal astrocytes demonstrated that injury-evoked changes to astrocyte gene expression occur acutely. We found 76 differentially expressed genes (DEGs) at P4, many of which are related to cell motility and cytoskeletal organization (Thbs1, Efemp1, Acta1, Acta2, Tpm2, Fgf14) but very few DEGs at P10 and P24. Lastly, we identified that microglial engulfment of astrocytes occurs in the developing dorsal horn, and that this process is altered by neonatal injury in a sex-dependent manner. These data illustrate, for the first time, that neonatal injury alters the postnatal development of spinal astrocytes.
2025-09-02 | GSE289540 | GEO
Project description:Analysis of gene expression by astrocytes or non-astrocyte cells in spinal cord injury (SCI) lesions may lead to the identification of molecules that impact on axon regrowth. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) from WT or STAT3-CKO astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples 14 days following SCI. DOI: 10.1038/nature17623 Young adult female mGFAP-Cre-RiboTag or mGFAP-Cre-RiboTag-STAT3-LoxP mice underwent severe crush SCI at thoracic level 10. 14 days following SCI, the central 3mm of the SCI lesion was extracted, homogenized and (i) astrocyte-specific ribosome-associated RNA (ramRNA) precipitated via a hemagglutinin (HA) tag targeted to either WT (n=4) or STAT3-CKO (n=3) astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples. Sex and age-matched mGFAP-Cre-RiboTag mice served as uninjured controls (n=4).
2016-03-30 | E-GEOD-76097 | biostudies-arrayexpress
Project description:Analysis of gene expression by astrocytes or non-astrocyte cells in spinal cord injury (SCI) lesions may lead to the identification of molecules that impact on axon regrowth. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) from WT or STAT3-CKO astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples 14 days following SCI. DOI: 10.1038/nature17623
2016-03-30 | GSE76097 | GEO
Project description:Glial spatial organization is critical for neural repair after spinal cord injury (SCI). In response to injury, reactive astrocytes extend hypertrophic processes to corral the lesion core and sequester debris and inflammatory cells. How these long, arborized processes remain intact, and how astrocytes avoid collisions to assemble a glial bridge to guide axon pathfinding across lesion site remain unclear. Here we identify the guidance receptor Plexin‑B1 as a key regulator of membrane integrity, process plasticity, and astrocyte alignment. Live‑cell imaging revealed that Plexin‑B1 deletion triggers membrane shedding and slows extension and retraction of astrocytic processes. The loss of astrocyte agility disrupts contact‑dependent avoidance, leading to disorganized astrocytes and misguided axons in vitro and in vivo. Mice with astrocyte‑specific Plexin‑B1 deletion showed defective glial border, enlarged lesions, inflammatory spill‑over, and dysregulated astrocyte–microglia signaling. These defects resulted in impaired axon regeneration and poorer functional recovery after spinal‑cord injury. Thus, Plexin‑B1 mediated agility of astrocyte processes safeguards membrane integrity and spatial alignment, enabling effective wound corralling and axon pathfinding during neural repair following SCI.
2025-09-16 | GSE304361 | GEO
Project description:Following contusive spinal injury astrocytes undergo inflammatory activation and proliferation in a process known as astrogliosis. Reactive astrocytes are attractive therapeutic targets as they sit central to many of the immune recruitment, injury response, and tissue healing processes of the spinal cord. However, methods of targeted expression of exogenous therapeutic genes within astrocytes must be validated to not alter the normal immunological involvement of astrocytes. To investigate the effect of transgene expression within astrocytes upon the immunological state of the contused cord, we injected the astrocyte-selective AAV5-GfaABC1D-dYFP reporter vector into an animal model of moderate contusive spinal cord injury. Bulk RNA microarrays were used to assess transcriptomic changes of the perilesional tissue.
2021-08-26 | GSE182796 | GEO
Project description:Adult zebrafish have the ability to recover from spinal cord injury and exhibit re-growth of descending axons from the brainstem to the spinal cord. We performed gene expression analysis using microarray to find damage-induced genes after spinal cord injury, which shows that Sox11b mRNA is up-regulated at 11 days after injury. However, the functional relevance of Sox11b for regeneration is not known. Here, we report that the up-regulation of Sox11b mRNA after spinal cord injury is mainly localized in ependymal cells lining the central canal and in newly differentiating neuronal precursors or immature neurons. Using an in vivo morpholino-based gene knockout approach, we demonstrate that Sox11b is essential for locomotor recovery after spinal cord injury. In the injured spinal cord, expression of the neural stem cell associated gene, Nestin, and the proneural gene Ascl1a (Mash1a), which are involved in the self-renewal and cell fate specification of endogenous neural stem cells, respectively, is regulated by Sox11b. Our data indicate that Sox11b promotes neuronal determination of endogenous stem cells and regenerative neurogenesis after spinal cord injury in the adult zebrafish. Enhancing Sox11b expression to promote proliferation and neurogenic determination of endogenous neural stem cells after injury may be a promising strategy in restorative therapy after spinal cord injury in mammals. Spinal cord injury or control sham injury was performed on adult zebrafish. After 4, 12, or 264 hrs, a 5 mm segment of spinal cord was dissected and processed (as a pool from 5 animals) in three replicate groups for each time point and treatment.
2010-10-19 | E-GEOD-20460 | biostudies-arrayexpress
Project description:Astrocytes in the spinal cord dorsal horn (SDH) play a pivotal role in synaptic transmission and neuropathic pain. However, the precise classification of SDH astrocytes in health and disease remains elusive. Here we reveal Gpr37l1 as a marker and functional regulator of spinal astrocytes. Through single-nucleus RNA sequencing, we identified Gpr37l1 as a selective GPCR marker for spinal cord astrocytes. Notably, SDH displayed reactive astrocyte phenotypes and exacerbated neuropathic pain following nerve injury combined with Gpr37l1 deficiency. In naïve animals, GPR37L1 knockdown in SDH astrocytes induces astrogliosis and pain hypersensitivity, while Gpr37l1-/- mice fail to recover from neuropathic pain. GPR37L1 activation by maresin-1 increased astrocyte GLT-1 activity and reduced spinal EPSCs and neuropathic pain. Selective overexpression of Gpr37l1 in SDH astrocytes reversed neuropathic pain and astrogliosis after nerve injury. Our findings illuminate astrocyte GPR37l1 as an essential negative regulator of pain, which protects neuropathic pain through astrocyte signaling in SDH.
2025-02-14 | GSE286467 | GEO
Project description:Comparison of genomic data from astrocytes and non-astrocyte cells from mice with or without FGF+EGF after SCI. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells, from spinal cord tissue of mice recieving i) SCI alone, ii) SCI+hydrogel depot containing FGF+EGF, or iii) SCI+empty hydrogel depot.
2018-09-20 | GSE111529 | GEO
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