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Lesion-remote astrocytes govern microglia-mediated white matter repair II

ABSTRACT: RNA sequencing was applied to examine changes in gene expression in astrocytes in spared tissue regions both rostral and caudal to the injury site in a mouse model of incomplete spinal cord injury (ISCI) over multiple post-injury time points. The RiboTag method was used to isolate astrocyte ribosome-associated mRNAs from the spinal cord of wild type mice and mice with astrocyte-specific conditional gene deletion (cKO) of a known transcriptional regulators of reactivity, STAT3 (Stat3 knockout: Stat3-cKO).

ORGANISM(S): Mus musculus

PROVIDER: GSE312871 | GEO | 2026/01/08

REPOSITORIES: GEO

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Lesion-remote astrocytes govern microglia-mediated white matter repair III

Project description:Single Nuclei RNA seq was used to examine gene expression of all spinal cord cell types from rostral and caudal spared regions of the injured spinal cord in a mouse model of incomplete spinal cord injury (iSCI, lateral hemisection) at multiple timepoints after injury (3, 7, 28 dpi). A focus of this study was to characterize spatiotemportal lesion-remote astrocyte gene expression via integration with paired spatial transcriptomics data.

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In vivo analysis of astrocyte ribosome-associated mRNA after traumatic spinal cord injury

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Lesion-remote astrocytes govern microglia-mediated white matter repair IV

Project description:Visium Spatial Transcriptomics was applied to spared tissue regions both rostral and caudal in a mouse model of incomplete spinal cord injuryt (ISCI) at multiple timepoints after injury (3,7,28dpi) to understand spatially distinct changes occuring in spared, yet reactive, spinal tissue after ISCI.

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Divergent transcriptional regulation of astrocyte reactivity across disorders [RNA-seq]

Project description:RNA sequencing was applied to examine changes in gene expression in reactive astrocytes following traumatic spinal cord injury (SCI) or neuroinflammatory insult by systemic administration of lipopolysaccharide (LPS). Transgenic Ribotag technology was used to isolate astrocyte ribosome-associated mRNAs from the spinal cord of wild type mice and mice with astrocyte-specific conditional gene deletion (cKO) of test-case transcriptional regulators of reactivity, SMARCA4 (Smarca4-astro-cKO) or STAT3 knockout (Stat3-astro-cKO). Examination of differentially expressed gene (DEG) profiles by upstream transcriptional regulator enrichment analysis (TREA) was used identify transcriptional regulators of reactivity in each condition. Together, findings from this study show that transcriptional changes associated with astrocyte reactivity are exquisitely heterogeneous and are customized from vast numbers of potential DEGs via context-specific combinatorial TR interactions. These data have also been made accessible in a open-access, searchable database: http://tr.astrocytereactivity.com

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Divergent transcriptional regulation of astrocyte reactivity across disorders [TR_ATAC_SCI]

Project description:Single-nuclei Assay for Transposase-Accessible Chromatin with sequencing (snATACseq) was applied to examine chromatin landscape changes and transcriptional regulator (TR) DNA motif accessibility in reactive astrocytes following traumatic spinal cord injury (SCI). Astrocyte nuclei were isolated from the spinal cord of wild type mice and mice with astrocyte-specific conditional gene deletion (cKO) of test-case TRs, SMARCA4 (Smarca4-astro-cKO) or STAT3 knockout (Stat3-astro-cKO). Comparison of differential chromatin accessibility revealed substantial remodeling during astrocyte reactivity, with more chromatin opening than closing. Marked alterations in access to SCI reactivity-associated TR motifs were also detected.

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In vivo analysis of astrocyte ribosome-associated mRNA after traumatic spinal cord injury

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Divergent transcriptional regulation of astrocyte reactivity across disorders [TR_ATAC_LPS]

Project description:Single-nuclei Assay for Transposase-Accessible Chromatin with sequencing (snATACseq) was applied to examine chromatin landscape changes and transcriptional regulator (TR) DNA motif accessibility in reactive astrocytes following neuroinflammatory insult by systemic administration of lipopolysaccharide (LPS). Astrocyte nuclei were isolated from the spinal cord of wild type mice and mice with astrocyte-specific conditional gene deletion (cKO) of test-case TRs, SMARCA4 (Smarca4-astro-cKO) or STAT3 knockout (Stat3-astro-cKO). Comparison of differential chromatin accessibility revealed substantial remodeling during astrocyte reactivity, with more chromatin opening than closing. Marked alterations in access to LPS reactivity-associated TR motifs were also detected.

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