Single‐cell RNA sequencing for traumatic spinal cord injury

Abstract

Traumatic spinal cord injury (tSCI) is a severe injury of the central nervous system (CNS) with complicated pathological microenvironment that results in hemorrhage, inflammation, and scar formation. The microenvironment of the injured spinal cord comprises heterogeneous neurons, glial cells, inflammatory cells, and stroma-related cells. Increasing evidence has indicated that the altered cellular and molecular microenvironment following tSCI is a key factor impeding functional recovery. Single-cell RNA sequencing (scRNA-seq) has provided deep insights into the dynamic cellular and molecular changes in the microenvironment by comprehensively characterizing the diversity of spinal cord cell types. Specifically, scRNA-seq enables the exploration of the molecular mechanisms underlying tSCI by elucidating intercellular communication in spinal cord samples between normal and injury conditions at a single-cell resolution. Here, we first described the pathological and physiological processes after tSCI and gave a brief introduction of the scRNA-seq technology. We then focused on the recent scRNA-seq researches in tSCI, which characterized diverse cell-type populations and specific cell-cell interactions in tSCI. In addition, we also highlighted some potential directions for the research of scRNA-seq in tSCI in the future.

Reactive astrogliosis in the era of single-cell transcriptomics

“…Neurotrauma and stroke represent another group of CNS disorders triggering substantial cellular heterogeneity that has been investigated by single-cell transcriptomics (Wilhelmsson et al, 2017;Moulson et al, 2021;Cao et al, 2022). Shi et al (2021) reported varying phagocytic properties of astrocytes in mouse models of hemorrhagic and ischemic strokes.…”

“…Neurotrauma and stroke represent another group of CNS disorders triggering substantial cellular heterogeneity that has been investigated by single-cell transcriptomics (Wilhelmsson et al, 2017 ; Moulson et al, 2021 ; Cao et al, 2022 ).…”

Noggin Protein can Induce the Differentiation of Rat Bone Marrow Mesenchymal Stem Cells to Neurons and Repair Spinal Cord Injury

“…The subsequent stage is characterized by secondary injury, where the spinal cord tissue experiences disrupted local blood circulation. The production of reactive oxygen, nitric oxide, and free fatty acids is neurotoxic, inducing prolonged damage to the local neurons and axons [25,26]. Therefore, in the control group, the diminishing NF200 mRNA content is attributed to the ongoing death of local neurons due to secondary injuries.…”

Tackling the glial scar in spinal cord regeneration: new discoveries and future directions

“…Astrocytes mount context-specific responses to CNS injuries ( Yu et al, 2020 ). For example, profiling astrocyte transcriptomes by microarray or single-cell RNA sequencing (scRNA-Seq) in stab wound injury, lipopolysaccharide (LPS)-induced neuroinflammation, ischemic stroke, SCI, and neurodegeneration reveals disease-specific gene expression ( Zamanian et al, 2012 ; Liddelow et al, 2017 ; Cao et al, 2022 ). Liddlelow et al categorized transcriptionally distinct astrocyte subsets into “A1” and “A2,” with opposing effects in various disease states: A1 astrocytes are pro-inflammatory and neurotoxic, whereas A2 astrocytes promote tissue repair and are neuroprotective.…”