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From the choroid plexus to the (sub)ventricular cells for oligodendrocyte (re)generation

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Resumo:Multiple sclerosis (MS) is an autoimmune demyelinating disorder that affects the central nervous system by damaging myelin and axons, but the exact cause of MS remains unclear. It is known that the immune system destroys oligodendrocytes (OLs), the myelinating cells of the CNS, and regardless of the efforts, it remains challenging to induce replacement of the lost OLs. The choroid plexus (CP) is fundamental for brain homeostasis as it secretes the cerebrospinal fluid. It is also a key modulator of neurogenesis and constitutes a site of neuroinflammation. Since MS is an inflammatory disorder, studying the relation between the CP and ventricular-subventricular zone (V-SVZ) is of interest. In this dissertation we explored the role of the CP in the modulation of neural stem cells and OLs progenitor cells (OPCs), located in the SVZ, in order to assess its potential to induce OL (re)generation. For that we used single cell RNA sequencing (scRNA-seq) data from both control and an MS model generated by our team. Here we explored the cell types, RNA velocities and cell-cell communication (CCC) inference. We have characterized the cell populations present in the V-SVZ of controls and MS model, and found differences in the clusters identified. RNA velocity revealed two central cores from where most of progenitor cells seamed to arise from, being one located at the neuronal intermediate progenitor cells cluster and the other one located in the astrocytes cluster. Further analysis has to be performed in order to confirm these results. Concerning CCC inference, we found evidence of signalling pathways between endothelial cells and pericytes with OPCs, which corroborates previous studies where this communication was reported. Together with literature, our data indicates that endothelial cells and pericytes regulate OPCs proliferation through Pdgf signalling. When analyzing the results from CCC inference in the CP-SVZ integrated data we found evidence of a communication from mesenchymal cells at the CP and ependymal cells through Wnt signalling. Another interaction was between OPCs and ependymal cells through TENASCIN signalling. Nevertheless, the existence of this interactions in vivo needs to be further validated.
Autores principais:Fernandes, Mónica da Silva
Assunto:scRNA-seq Multiple Sclerosis Choroid plexus Subventricular zone Oligoden-drocytes Esclerose Múltipla Zona subventricular Oligodendrócitos
Ano:2023
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho

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