Falque Marie, Magalon Karine, Gil Florian, Durbec Pascale
Aix Marseille University, CNRS, IBDM, Marseille, France.
iScience. 2025 Jul 31;28(9):113255. doi: 10.1016/j.isci.2025.113255. eCollection 2025 Sep 19.
After brain insults, neuronal progenitors of the adult mouse sub-ventricular zone can change migration mode to emigrate toward lesioned tissues and participate in regenerative processes. During demyelination, these progenitors change fate to generate oligodendrocytes that contribute to myelin replacement. Herein, we examined the possible link between neuroblast behavior and mechanical tissue properties. Using sub-ventricular zone organotypic explant, we found that matrix stiffness influences neuroblast migratory mode and fate. A softer matrix promotes a switch from collective (chain) to isolated cell migration and reprogramming into oligodendrocytes. Nanoindentation on fresh brain slices provided evidence for changes in the mechanical properties of the corpus callosum following lysophosphatidylcholine-induced focal demyelination. In particular, we propose that the decrease in stiffness may be due to myelin loss and extracellular matrix modification. Overall, our work suggests that postlesional changes in mechanical cues regulate neuroblast mobilization and fate conversion in the adult mammalian central nervous system.
在脑部受到损伤后，成年小鼠脑室下区的神经前体细胞可以改变迁移模式，向受损组织迁移并参与再生过程。在脱髓鞘过程中，这些前体细胞会改变命运，生成有助于髓鞘替代的少突胶质细胞。在此，我们研究了神经母细胞行为与机械组织特性之间的可能联系。利用脑室下区器官型外植体，我们发现基质硬度会影响神经母细胞的迁移模式和命运。较软的基质会促使迁移模式从集体（链式）转变为单个细胞迁移，并促使细胞重编程为少突胶质细胞。对新鲜脑片进行纳米压痕实验，为溶血磷脂酰胆碱诱导的局灶性脱髓鞘后胼胝体机械特性的变化提供了证据。特别是，我们认为硬度的降低可能是由于髓鞘丢失和细胞外基质改变所致。总体而言，我们的研究表明，损伤后机械信号的变化调节了成年哺乳动物中枢神经系统中神经母细胞的动员和命运转换。
