Aix Marseille Univ, CNRS, Developmental Biology Institute of Marseille (IBDM), IBDM-UMR 7288, Case 907, Parc Scientifique de Luminy, Marseille Cedex 09 13288, France.
Aix Marseille Univ, CNRS, Developmental Biology Institute of Marseille (IBDM), IBDM-UMR 7288, Case 907, Parc Scientifique de Luminy, Marseille Cedex 09 13288, France.
Stem Cell Reports. 2021 Jul 13;16(7):1792-1804. doi: 10.1016/j.stemcr.2021.05.002. Epub 2021 Jun 3.
In response to corpus callosum (CC) demyelination, subventricular zone-derived neural progenitors (SVZdNPs) are mobilized and generate new myelinating oligodendrocytes (OLG). Here, we examine the putative immunomodulatory properties of endogenous SVZdNPs during demyelination in the cuprizone model. SVZdNP density was higher in the lateral and rostral CC regions, and demyelination was inversely correlated with activated microglial density and pro-inflammatory cytokine levels. Single-cell RNA sequencing showed that CC areas with high levels of SVZdNP mobilization were enriched in a microglial cell subpopulation with an immunomodulatory signature. We propose MFGE8 (milk fat globule-epidermal growth factor-8) and β3 integrin as a ligand/receptor pair involved in dialogue between SVZdNPs and microglia. Immature SVZdNPs mobilized to the demyelinated CC were found highly enriched in MFGE8, which promoted the phagocytosis of myelin debris in vitro. Overall, these results demonstrate that, in addition to their cell replacement capacity, endogenous progenitors have immunomodulatory properties, highlighting a new role for endogenous SVZdNPs in myelin regeneration.
针对胼胝体（CC）脱髓鞘，室下区源性神经前体细胞（SVZdNPs）被动员并产生新的髓鞘形成少突胶质细胞（OLG）。在这里，我们在杯状朊病毒模型中研究了内源性 SVZdNP 在脱髓鞘过程中的潜在免疫调节特性。SVZdNP 密度在侧脑室和额 CC 区域较高，脱髓鞘与激活的小胶质细胞密度和促炎细胞因子水平呈负相关。单细胞 RNA 测序显示，具有高水平 SVZdNP 动员的 CC 区域富含具有免疫调节特征的小胶质细胞亚群。我们提出 MFGE8（乳脂肪球-表皮生长因子-8）和β3 整合素作为参与 SVZdNP 和小胶质细胞之间对话的配体/受体对。在脱髓鞘的 CC 中动员的未成熟 SVZdNP 高度富含 MFGE8，这促进了体外髓鞘碎片的吞噬作用。总体而言，这些结果表明，除了它们的细胞替代能力外，内源性祖细胞还具有免疫调节特性，突出了内源性 SVZdNP 在髓鞘再生中的新作用。
