Stefano Pluchino, University of Cambridge, Cambridge, United Kingdom

Defining the heterogeneity of non-neuronal immune CELLular responses

Funded in: 2021, 2022, 2023


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Problem: Lack of effective restorative treatments
Target: Define the role of microglia and macrophages
Goal: Unravel how inflammation exacerbates the pathology

Traumatic spinal cord injury (SCI) is a debilitating central nervous system (CNS) pathology that has yet to be fully understood and thus lacks effective restorative treatments. Unlike non-CNS wounds, SCI wounds fail to heal completely. This results in a chronic wound characterized by persistent inflammation, which is driven by both CNS-resident microglia (MG) and CNS-infiltrating macrophages (Mφ). However, the precise roles of these two cell-types after SCI remain unclear because after entering the CNS, Mφ take on the morphology and transcriptional profiles of MG, making the two populations difficult to distinguish.
The researchers plan to separate MG and Mφ using an innovative experimental model that fluorescently labels MG and Mφ, by taking advantage of the difference in the lifespan of these two cell types. In addition, the scientists aim to map the changes in gene expression of MG and Mφ over time in experimental spinal cord injury (SCI) at an unprecedented resolution by employing the cutting-edge technique, single-cell RNA sequencing (scRNAseq). The data generated from CELL_seq will compliment and build upon the existing knowledge of reactive MG and Mφ cells after SCI. Furthermore, the neuroscientists will make this data publicly available through an interactive website. This will help to unravel how inflammation exacerbates the pathology and to provide a resource from which to optimise future therapeutic approaches.