Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons

Matson, Kaya J.E.; Russ, D.; Kathe, Claudia; Hua, Isabelle; Maric, Dragan; Ding, Yi; Krynitsky, Jonathan; Pursley, Randall; Sathyamurthy, Anupama; Squair, Jordan W.; Courtine, Grégoire; Levine, Ariel J.

doi:10.1038/s41467-022-33184-1

Cited by 55 publications

(47 citation statements)

References 91 publications

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“…These clusters were defined using a human brain DropNc-seq dataset, 38 and included microglia, oligodendrocytes, oligodendrocyte precursor cells (OPCs), astrocytes, endothelial cells, neurons, and neuronal stem cells (NSCs) (Figure 6b and 6c). The negative selection strategy enriched microglial nuclei to ~40% of the sample, compared to ~3.7% collected from whole mouse spinal tissue in other studies 39 (Figure 6b). Microglial nuclei clusters expressed known marker genes described in previous studies including ITGAM, CTSS, CSF1R and C1QA (Figure 6d).…”

Section: Human Dorsal Horn Spinal Microglia Exhibit Heterogeneous Cel...mentioning

confidence: 78%

Newly repopulated spinal cord microglia exhibit a unique transcriptome and correlate with pain resolution

Donovan

Bridges

Nippert

et al. 2022

Preprint

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Microglia contribute to the initiation of pain, however, a translationally viable approach addressing how or when to modulate these cells remains elusive. We used a targeted, inducible genetic microglial depletion strategy at both the acute and acute-to-chronic transition phases in the clinically-relevant tibial fracture/casting model to determine the contribution of microglia to the initiation and maintenance of pain. We observed complete resolution of pain after transient microglial depletion at the acute-to-chronic phase, which coincided with the timeframe of full repopulation of microglia. These repopulated microglia were morphologically distinct from control microglia, suggesting they may exhibit a unique transcriptome. RNA sequencing of repopulated spinal cord microglia identified genes of interest using weighted gene co-expression network analysis (WGCNA). We intersected these genes with a newly-generated single nuclei microglial dataset from human dorsal horn spinal cord to identify human-relevant genes that may promote homeostatic features of microglia and ultimately promote pain resolution after injury.

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Section: Human Dorsal Horn Spinal Microglia Exhibit Heterogeneous Cel...mentioning

confidence: 78%

Newly repopulated spinal cord microglia exhibit a unique transcriptome and correlate with pain resolution

Donovan

Bridges

Nippert

et al. 2022

Preprint

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“…Single cell transcriptomics. More recent transcriptome work in the SCI field has included studies utilizing single cell RNA-Seq (scRNA-Seq) [98,[110][111][112][113][114][115][116], including a recent atlas of spinal cord injury in mice [114]. Due to the complexities of scRNA-Seq data, including cell typing and the disparity between limited sample numbers and large numbers of cells per sample, as well as a different modality for viewing scRNA-Seq data, we chose not to include that data at this time to focus on the more broadly available bulk RNA-Seq datasets.…”

Section: Discussionmentioning

confidence: 99%

Construction of a searchable database for gene expression changes in spinal cord injury experiments

Rouchka

Almeida

House

et al. 2023

Preprint

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Spinal cord injury (SCI) is a debilitating disease resulting in an estimated 18,000 new cases in the United States on an annual basis. Significant behavioral research on animal models has led to a large amount of data, some of which has been catalogued in the Open Data Commons for Spinal Cord Injury (ODC-SCI). More recently, high throughput sequencing experiments have been utilized to understand molecular mechanisms associated with SCI, with nearly 6,000 samples from over 90 studies available in the Sequence Read Archive. However, to date, no resource is available for efficiently mining high throughput sequencing data from SCI experiments. Therefore, we have developed a protocol for processing RNA-Seq samples from high-throughput sequencing experiments related to SCI resulting in both raw and normalized data that can be efficiently mined for comparisons across studies as well as homologous discovery across species. We have processed 1,196 publicly available RNA-seq samples from 50 bulk RNA-Seq studies across nine different species, resulting in an SQLite database that can be used by the SCI research community for further discovery. We provide both the database as well as a web-based front-end that can be used to query the database for genes of interest, differential gene expression, genes with high variance, and gene set enrichments.

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“…4). The core reactivity signature is shared in glial populations across pathologies including AD 36,37,[44][45][46] , multiple sclerosis 41,42 , aging 43 , spinal cord injury 24,30,67,71 and recently ischemic stroke 40,72 , indicating conserved aspects of activation 34,69 . In accordance, our reference-free deconvolution identified injury-related topics of expression programs enriched for profiles of disease-associated astrocytes and of oligodendrocytes (Fig.…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal transcriptomic map of ischemic brain injury

Žucha

Abaffy

Kirdajová

et al. 2023

Preprint

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The role of non-neuronal cells in the resolution of cerebral ischemia remains to be fully understood. To decode key cellular processes that occur after ischemia, we performed spatial and single-cell transcriptomic profiling of mouse brain tissue during the first week of injury. Cortical gene expression was severely disrupted, being defined by inflammation and cell death in the lesion core, and glial scar formation on the periphery. For each of the three major glial populations, an inflammatory-responsive state, resembling the reactive states observed in neurodegenerative contexts, was documented. The recovered spectrum of ischemia-induced oligodendrocyte states supports the emerging hypothesis that oligodendrocytes actively respond to and modulate the neuroinflammatory stimulus. Thus, we present a landmark transcriptomic dataset that provides a comprehensive view of spatiotemporal organization of processes in the post-ischemic brain and documents the conservation of glial response in CNS pathology.

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Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons

Cited by 55 publications

References 91 publications

Newly repopulated spinal cord microglia exhibit a unique transcriptome and correlate with pain resolution

Newly repopulated spinal cord microglia exhibit a unique transcriptome and correlate with pain resolution

Construction of a searchable database for gene expression changes in spinal cord injury experiments

Spatiotemporal transcriptomic map of ischemic brain injury

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