Mouthon Marc-André, Morizur Lise, Dutour Léa, Pineau Donovan, Kortulewski Thierry, Boussin François D
Université de Paris and Université Paris-Saclay, Inserm, LRP/iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, 92265 Fontenay-aux-Roses, France.
iScience. 2020 Nov 7;23(12):101784. doi: 10.1016/j.isci.2020.101784. eCollection 2020 Dec 18.
The production of neurons from neural stem cells (NSCs) persists throughout life in the mouse ventricular-subventricular zone (V-SVZ). We have previously reported that NSCs from adult V-SVZ are contained in cell populations expressing the carbohydrate SSEA-1/LeX, which exhibit either characteristics of quiescent NSCs (qNSCs) or of actively dividing NSCs (aNSCs) based on the absence or the presence of EGF-receptor, respectively. Using the fluorescence ubiquitination cell cycle indicator-Cdt1 transgenic mice to mark cells in G/G phase of the cell cycle, we uncovered a subpopulation of qNSCs which were primed to enter the cell cycle . Besides, we found that treatment with Syndecan-1, a heparan sulfate proteoglycan involved in NSC proliferation, hastened the division of qNSCs and increased proliferation of aNSCs shortening their G phase . Furthermore, administration of Syndecan-1 ameliorated the recovery of neurogenic populations in the V-SVZ after radiation-induced injury providing potential cure for neurogenesis decline during brain aging or after injury.
在小鼠脑室下区（V-SVZ），神经干细胞（NSC）生成神经元的过程在其一生中持续存在。我们之前报道过，成年V-SVZ的神经干细胞包含在表达碳水化合物SSEA-1/LeX的细胞群体中，这些细胞群体根据是否存在表皮生长因子受体，分别表现出静止神经干细胞（qNSC）或活跃分裂神经干细胞（aNSC）的特征。利用荧光泛素化细胞周期指示剂-Cdt1转基因小鼠标记处于细胞周期G/G期的细胞，我们发现了一群准备进入细胞周期的静止神经干细胞亚群。此外，我们发现，用参与神经干细胞增殖的硫酸乙酰肝素蛋白聚糖Syndecan-1处理，可加速静止神经干细胞的分裂，并增加活跃分裂神经干细胞的增殖，缩短其G期。此外，给予Syndecan-1可改善辐射诱导损伤后V-SVZ神经源性群体的恢复，为脑衰老或损伤后神经发生减少提供了潜在的治疗方法。
