Project description
Spinal cord injury: immune cell-neural stem cell interplay
As with most tissues, the central nervous system contains an endogenous pool of neural stem cells (NSCs). However, these cells do not seem to generate neurons in vitro or in mammalian models, suggesting that the cues from the environment prevent them from assuming a neuronal fate. Funded by the Marie Skłodowska-Curie Actions programme, the SCIENSC project aims to investigate the role of the immune cells in shaping the microenvironment following spinal cord injury. Researchers will study how immune cells interact with and influence endogenous NSCs after injury. The project has the potential to identify key mechanisms that can be modulated to improve the neuronal differentiation capacity of NSCs after injury, triggering recovery.
Objective
Despite endogenous neural stem cells (eNSCs) being present in the adult mammalian central nervous system (CNS), their neuronal potential upon injury is rarely achieved in the brain and never in the spinal cord (SC) environment. This makes widespread SC injuries (SCIs) especially challenging to treat. Even though SC eNSCs give rise to astrocytes, oligodendrocytes, and neurons in vitro, they almost exclusively generate glial scar-forming astrocytes, seldom myelinating oligodendrocytes, and never neurons in mammalian models. We still do not know the exact SC niche cues preventing eNSCs from efficiently assuming oligodendrocyte and neuronal fates, averting a functional SC healing. Notably, SCI induces a vast immune response and I hypothesise that immune cells that are responsive to the SCI, contribute to eNSC niche formation, where they can exert an effect on eNSC regulation. I will investigate this by unravelling (O1) temporal, heterogenous immune responses to the SCI and (O2) their spatial interplay with the eNSCs using advanced methodologies, such as spectral flow cytometry and spatial transcriptomics. This will enable me to identify which of these immune cells affect eNSC gene regulatory networks leading to instigation of astrocyte but not oligodendrocyte or neuronal fates. Finally, (O3) I will identify SCI-specific enhancer elements of the immune cells of interest by comparing chromatin signatures of these immune cell types located across different tissues. This knowledge will present a ‘divide and conquer’ opportunity – to compartmentalise and disconnect immune system across different tissues enabling a targeted immune cell manipulation specifically within the SCI environment. The long-term outcome of this project will help the design of enhancer-based immuno-modulatory therapies to dictate eNSC fates and generate oligodendrocytes and neurons in vivo leading to a functional SCI recovery.
Fields of science
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
17177 Stockholm
Sweden