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

最近的证据表明，成人神经干/祖细胞（ANSC）分泌自分泌/旁分泌因子，并且这些内在因子参与成人神经发生的维持。我们利用信号序列捕获法从成年海马神经干/祖细胞中鉴定出一种新的分泌分子--干细胞源性神经干/祖细胞支持因子（stemcell-derived neural stem/progenitor cell supporting factor，SDNSF）。SDNSF在成年人中枢神经系统中的表达定位于海马，包括齿状回，在那里神经发生持续终生。在缺血处理海马的诱导神经发生状态中，SDNSF的表达上调。作为功能方面，SDNSF蛋白在碱性成纤维细胞生长因子2（FGF-2）撤除后为ANSC提供剂量依赖性存活效应。在没有FGF-2的情况下，SDNSF处理的ANSC也保留了自我更新潜力和多能性。然而，SDNSF没有促有丝分裂活性，也不是促进FGF-2促有丝分裂作用的辅助因子。提示SDNSF作为一种自分泌/旁分泌因子在维持成体中枢神经系统干细胞潜能和终身神经发生中具有重要作用。

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.