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Poster De Conférence Année : 2019

Immunomodulatory functions of endogenous neural stem cells for myelin repair

Résumé

Do endogenous neural stem cells contribute to myelin repair through immunomodulation? In response to an acute corpus callosum (CC) demyelination, subventricular zone-derived neural progenitors (SVZdNP) migrate to the demyelinated CC to replace dead oligodendrocytes. This mobilization is regionalized, with preferential recruitment in the rostro-lateral CC compared to postero-medial CC (Brousse et al., 2015; Xing et al., 2014). Interestingly, areas with high SVZdNP mobilization correspond to those less affected by cuprizone-induced demyelination. Although the majority of SVZdNP recruited in the demyelinated CC adopt oligodendrocyte identity, some stay undifferentiated and could protect the CC from demyelination and/or promote remyelination through immunomodulation. Indeed, several studies showed that transplantation of neural stem cells improve functional recovery in many pathological contexts, and do so mainly through immunomodulation (reviewed in Kokaia et al., 2012). In our demyelination model, we observe more activated microglia in areas where SVZdNP are poorly recruited (postero-medial CC) and a more aggressive inflammatory profile. Thus we analyzed whether endogenous SVZdNP spontaneously recruited to the demyelinated CC could dialog with microglial cells to modulate their inflammatory properties and exert protective functions. Using genetic tracing we sorted SVZdNPs and microglia in demyelinated CC and single cell RNA drop sequencing we searched for ligand-receptor couples implicated in SVZdNP/microglia dialog. We identified MFGE8 secreted by SVZdNP and integrin β3 expressed by microglial cells as a couple implicated in cell-cell interactions to promote myelin debris phagocytosis, a prerequisite for myelin repair.
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Dates et versions

hal-02445858 , version 1 (23-01-2020)

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  • HAL Id : hal-02445858 , version 1

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Pascale Durbec, Myriam Cayre, Béatrice Brousse. Immunomodulatory functions of endogenous neural stem cells for myelin repair. 14th European Meeting on Glial Cells in Health and Disease (GLIA), Jul 2019, Porto, Portugal. ⟨hal-02445858⟩
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