Isolation and characterization of stem cell-derived neural stem/progenitor cell supporting factor, SDNSF.

最近的证据表明，成体神经干/祖细胞(ANSCs)分泌自分泌/旁分泌因子，这些内在因子参与了成体神经发生的维持。我们用信号序列捕捉法从成年大鼠海马神经干/祖细胞S中鉴定出一个新的分泌分子--干细胞源性神经干/祖细胞支持因子(SDNSF)。SDNSF在成年中枢神经系统中的表达定位于海马区，包括海马齿状回，海马齿状回的神经发生贯穿终生。在脑缺血处理后的诱导神经发生状态下，SDNSF的表达上调。作为功能方面，SDNSF蛋白为停用碱性成纤维细胞生长因子2(FGF-2)后的ANSC提供了剂量依赖的生存效应。在缺乏成纤维细胞生长因子-2的情况下，SDNSF处理的ANSCs也保留了自我更新的潜力和多能性。然而，SDNSF不具有促分裂活性，也不是促进成纤维细胞生长因子-2促分裂作用的辅因子。这些结果提示SDNSF作为一种自分泌/旁分泌因子在维持成人中枢神经系统的干细胞潜能和终生神经发生中起着重要作用。

Recent evidences suggests that adult neural stem/progenitor cells (ANSCs) secrete autocrine/paracrine factors and that these intrinsic factors are involved in the maintenance of adult neurogenesis. We identified a novel secretory molecule, stem cell-derived neural stem/progenitor cell supporting factor (SDNSF), from adult hippocampal neural stem/progenitor cell s by using the signal sequence trap method. The expression of SDNSF in adult central nervous system was localized to hippocampus including dentate gyrus, where the neurogenesis persists throughout life. In induced neurogenesis status seen in ischemically treated hippocampus, the expression of SDNSF was up-regulated. As functional aspects, SDNSF protein provided a dose-dependent survival effect for ANSC following basic fibroblast growth factor 2 (FGF-2) withdrawal. ANSCs treated by SDNSF also retain self-renewal potential and multipotency in the absence of FGF-2. However, SDNSF did not have mitogenic activity, nor was it a cofactor that promoted the mitogenic effects of FGF-2. These data suggested an important role of SDNSF as an autocrine/paracrine factor in maintaining stem cell potential and lifelong neurogenesis in adult central nervous system.