ScRNA-sequence of NeuroD1-astrocyte therapy post-TBI mouse
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE316172 | GEO | 2026/01/15
REPOSITORIES: GEO
Similar Datasets
Project description:Astrocytes, the most abundant glial cells in the central nervous system (CNS), play a critical role in brain injury responses. While NeuroD1 overexpression in astrocytes has been shown to reverse glial scar formation and promote tissue repair in mouse models of traumatic brain injury (TBI), the underlying molecular mechanisms remain incompletely understood. To address this, we performed single-cell transcriptomic analysis on a controlled cortical impact (CCI) mouse model using recombinant adeno-associated virus (rAAV)-mediated astrocyte-specific NeuroD1 overexpression.Our findings demonstrate that NeuroD1 overexpression suppresses microglial activation and mitigates brain damage post-TBI. Single-cell RNA sequencing revealed significant shifts in astrocyte subtypes, with upregulated neuroinflammatory pathways and downregulated oxygen metabolism in TBI mice. Conversely, NeuroD1 overexpression reshaped astrocyte subpopulation dynamics, enhanced oxygen metabolism-related gene expression, and attenuated neuroinflammatory signaling. This study provides a comprehensive transcriptomic dataset detailing cellular and astrocyte subtype-specific changes following NeuroD1-mediated brain repair. These insights advance our understanding of cell fate modulation in TBI and support the development of NeuroD1-based gene therapies, offering a valuable resource for future TBI research and therapeutic strategies.
2025-11-01 | GSE305371 | GEO
Project description:scRNA-seq of NeuroD1-astrocyte therapy post-TBI mouse
| PRJNA1305420 | ENA
Project description:CNS injury results in chronic scar formation that interferes with function and inhibits repair. Extracellular matrix (ECM) is prominent in the scar and potently regulates cell behavior. However, comprehensive information about the ECM proteome is largely lacking, and region- as well as injury-specific differences are often not taken into account. These aspects are the focus of our perspective on injury and scar formation. To highlight the importance of such comprehensive proteome analysis we include data obtained with novel analysis tools of the ECM composition in the scar and show the contribution of monocytes to the ECM composition after traumatic brain injury (TBI). Monocyte invasion was reduced using the CCR2-/- mouse line and step-wise de-cellularization and proteomics allowed determining monocyte-dependent ECM composition and architecture of the glial scar. We find significant reduction in the ECM proteins Tgm1, Itih (1,2, and 3), and Ftl in the absence of monocyte invasion. We also describe the scar ECM comprising zones with distinctive composition and show a subacute signature upon comparison to proteome obtained at earlier times after TBI. These results are discussed in light of injury-, region- and time-specific regulation of scar formation highlighting the urgent need to differentiate injury conditions and CNS-regions using comprehensive ECM analysis.
2020-05-27 | PXD017478 | Pride
Project description:Direct astrocyte-to-neuron conversion holds promise for in situ neuroregeneration to treat neurodegenerative diseases. However, commonly-used adeno-associated vectors carrying GFAP mini-promoters drive leaky expression of neurogenic factors in endogenous neurons, raising concerns about trans-differentiation validity. Developing inducible, lineage-traceable transgenic mice, we evaluate NeuroD1 effects on astrocyte-to-neuron conversion in spinal cord and brain injury models. Lineage-tracing and single-cell transcriptomics reveal that ectopic NeuroD1 expression promotes robust conversion of reactive astrocytes in lesion cores to neurons at the acute phase of injury, but not in peri-injury astrocytes.
2025-06-18 | GSE290098 | GEO
Project description:Scar formation after brain injury is still ill understood. Here we examined the interplay between astrocyte proliferation and monocyte invasion. Using genetic mouse models to decrease or increase reactive astrocyte proliferation, we demonstrate inverse effects on monocyte numbers in the injury site, with e.g. reduced monocyte numbers when astrocyte proliferation was increased. Conversely, reducing monocyte invasion using CCR2-/- mice causes a strong increase in astrocyte proliferation, demonstrating an intriguing negative cross-regulation between these cell types at the vascular interface. CCR2-/- mice showed reduced scar formation with less extracellular matrix deposition, smaller lesion site and increased neuronal coverage. Surprisingly, also the GFAP+ scar area was significantly decreased despite increased astrocyte proliferation. Proteomic analysis at the peak of increased astrocyte proliferation revealed a decrease in ECM synthesizing enzymes in the injury sites of CCR2-/- mice already at this stage, highlighting how early key aspects of scar formation are initiated. Taken together we provide key novel insights into the cross-regulation of juxtavascular proliferating astrocytes and invading monocytes as a key mechanism of scar formation upon brain injury.
2018-04-16 | PXD008906 | Pride
Project description:Traumatic brain injury (TBI) is a complex condition in which multiple pathophysiological mechanisms influence the course of the disease. After the primary mechanical impact, neuroinflammatory reactions of glial cells along with infiltrating peripheral immune cells mainly determine the overall clinical outcome. However, these secondary processes and their molecular determinants promoting either beneficial or detrimental consequences are not well-defined. Here, we show that TBI-mediated NF-κB activation in astrocytes impairs their homeostatic functions and acts as a key regulator of multiple post-traumatic responses in mice. We determined striking deficits in CNS scar formation after TBI using a combination of NF-κB-reporter mice, conditional mouse models allowing astrocytic NF-κB modulation, and analysis of transcriptomic signatures. Importantly, the development of wound healing deficits depends on paracrine signaling of NF-κB-activated astrocytes and cross-responsive microglial cells.Our findings identify astrocytic NF-κB activation as a critical pathological amplification factor interfering with the restoration of CNS integrity at wound lesion sites.
2026-01-20 | GSE276422 | GEO
Project description:Traumatic brain injury (TBI) is a complex condition in which multiple pathophysiological mechanisms influence the course of the disease. After the primary mechanical impact, neuroinflammatory reactions of glial cells along with infiltrating peripheral immune cells mainly determine the overall clinical outcome. However, these secondary processes and their molecular determinants promoting either beneficial or detrimental consequences are not well-defined. Here, we show that TBI-mediated NF-κB activation in astrocytes impairs their homeostatic functions and acts as a key regulator of multiple post-traumatic responses in mice. We determined striking deficits in CNS scar formation after TBI using a combination of NF-κB-reporter mice, conditional mouse models allowing astrocytic NF-κB modulation, and analysis of transcriptomic signatures. Importantly, the development of wound healing deficits depends on paracrine signaling of NF-κB-activated astrocytes and cross-responsive microglial cells. Our findings identify astrocytic NF-κB activation as a critical pathological amplification factor interfering with the restoration of CNS integrity at wound lesion sites.
2026-01-20 | GSE276182 | GEO
Project description:Traumatic brain injury (TBI) is a major cause of long-term neurological impairment, with aging amplifying vulnerability and worsening recovery. Older individuals face greater cognitive and motor deficits post-TBI and respond less effectively to treatments, as both aging and TBI independently elevate neuroinflammation and cognitive decline. This study evaluated the therapeutic effects of human adipose-derived stem cell small extra-cellular vesicles (hASC-sEVs) on neurological recovery and neuroinflammation in a mouse model of TBI. Male C57BL/6 mice (3, 15, and 20 months old) underwent controlled cortical impact (CCI) and received intranasal hASC-sEVs 48 h post-injury; control groups received PBS. A dose–response study at 7 days post injury (dpi) identified 20 µg as the optimal therapeutic dose, improving motor function, reducing neuroinflammation, and enhancing neurogenesis. This was followed by a 30-dpi study assessing cognitive function, neuroinflammation, neurogenesis, and proteomic changes in microglia and astrocytes via mass spectrometry. hASC-sEV treatment significantly improved behavioral out-comes and reduced neuroinflammatory markers (GFAP, IBA-1, and MHC-II), with re-duced efficacy observed in older mice. Proteomics revealed that hASC-sEVs reduce in-flammatory proteins (TNF-α, IL-1β, IFNG, CCL2) and modulated mitochondrial dysfunction and reactive oxygen species. These results highlight hASC-sEVs as a promising cell-free therapy for improving TBI outcomes, especially in aging populations.
2025-09-11 | PXD067584 | Pride
Project description:The variations of psycho- and physiological deficits caused by TBI correlate with the degree of brain injury. However, the objective stratification of TBI is yet elusive. A modified closed-head injury Marmarou model was used based on the release of a 500 gram steel slug on top of the rat skull from a height of 100 cm or 120 cm to induce differential injury models for mild TBI and moderate TBI, respectively. The skull was covered by a helmet to mimic the warfighter’s condition in theater. The hippocampus was at the focal point of injury, and the cerebellum, was susceptible to diffused shock (secondary injury). The HC-CB axis coordinates visuomotor performance, which is known to be vulnerable to TBI. The rats that received moderate TBI showed deficient visuomotor performance by the Barnes maze test for longer time periods than those inflicted with mild TBI. The time resolved and HC-CB specific transcriptomic analysis focused on genes that enabled discrimination of mild from moderate TBI at 14d post injury which is equivalent to nearly 1.5 years of human lifetime. The functional analysis elucidated an active healing mechanism in the HC exposed to mild TBI. In contrast, moderate TBI caused delayed healing and active cell death in the HC. In conclusion, the graded brain injuries differentially implicated the HC-CB axis, despite the use of a helmet to reduce the impact. Time resolved functional dynamics informed the distinct consequences of mild vs. moderate TBI.
2020-12-31 | GSE131435 | GEO
Project description:We inflicted TBI to chemokine-deficient mouse lines in order to establish involvement of various signalling pathways that may be addressed therapeutically. Interacting chemokine pathways in brain regulate distinct inflammatory cells. Activated microglia are separate from invading phagocytes and dendritic cells. Findings show potential targets to interfere with specific inflammatory responses after brain injury. TBI was carried out in Ccl3-/- and Ccr2-/- mice, total RNA prepared from injured cerebral neocortex after three days. RNA samples were from uninjured Ccl3-/- and Ccr2-/- mice as reference for hybridization on Affymetrix microarrays.
2014-06-14 | E-GEOD-58483 | biostudies-arrayexpress