Identification of spinal cord immune niche interactions dictating endogenous neural stem cell fates upon injury

NAISS 2023/22-905


NAISS Small Compute

Principal Investigator:

Martyna Lukoseviciute


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

30108: Cell and Molecular Biology




Despite neural stem cells (NSCs) being present in the adult mammalian central nervous system, their neuronal potential upon injury is rarely achieved in the brain and never in the spinal cord (SC) environment. This makes SC injuries (SCIs) especially challenging to treat. Ependymal cells (ECs), residing by the central canal in the SC, give rise to migratory progeny exhibiting NSC qualities upon injury. Even though ECs give rise to astrocytes, oligodendrocytes and neurons in vitro, they almost exclusively generate scar-forming astrocytes, seldom oligodendrocytes and never neurons in mouse models. We still do not know the exact SC niche cues preventing EC-derived NSCs from efficiently assuming oligodendrocyte and neuronal fates. Notably, SCI induces a vast immune response and I hypothesise that this formed dynamic SC immune niche regulates NSC differentiation and intervenes with their oligodendrocyte and neuronal fates. Therefore, I will investigate which immune cells interact with EC-derived NSCs and affect their gene regulatory networks leading to instigation of astrocyte but not oligodendrocyte or neuronal fates. Curiously, zebrafish encompasses a similar immune system to mammalians but can regenerate SCI due to ECs being able to give rise to glial and neuronal cells. Therefore, I will compare the mouse NSC-immune niche with that of zebrafish SCI model. Integration of such information will provide an overview of a pro-regenerative SC niche, where EC progeny can reach their full potential. The project outcome will help the design of modulatory neuroimmune-regeneration therapies to dictate endogenous EC fates towards oligodendrocytes and neurons upon SCI in mammals.