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

干细胞源性神经干/祖细胞支持因子 SDNSF 的分离和表征。

• 批准号: 13470036
• 负责人: TASHIRO Kei
• 金额: $ 9.22万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470036/
• 关键词: stem cell; inner ear; secreted molecule; signal-sequence trap; otocyst; soluble factor; rat; development; 生存支持因子; 幹細胞由来神経生存因子; SDNSF; 分泌タンパク; カルシウム依存性; 遺伝子欠損マウス; 細胞生存支持活性; MTTアッセイ; タンパク精製; ポリクローナル抗体; 細胞増殖因子

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.

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，这些内在因素参与维持成人神经发生。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。这些数据表明SDNSF作为自分泌/旁分泌因子在维持成人中枢神经系统干细胞潜力和终生神经发生方面发挥着重要作用。

项目成果

Kanazawa, N., Okazaki, T., Nishimura.H., Tashiro K., Inaba K., Miyachi, Y.: "DCIR acts as an inhibitory receptor depending on its immunoreceptor tyrosine-based inhibitory motif"J. Invest. Dermatol.. 118. 261-266 (2002)

Kanazawa, N.、Okazaki, T.、Nishimura.H.、Tashiro K.、Inaba K.、Miyachi, Y.：“DCIR 根据其基于免疫受体酪氨酸的抑制基序发挥抑制性受体作用”。

Kobuke, K., Furukawa, Y., Sugai, M., Tanigaki, K., Ohashi, N, Matsumori, A., Sasayama, S., Honjo, T., Tashiro, K.: "ESDN, a novel neuropilin-like membrane protein cloned from vascular cells with the longest secretory signal sequence among eukaryotes is up

Kobuke, K.、Furukawa, Y.、Sugai, M.、Tanigaki, K.、Ohashi, N、Matsumori, A.、Sasayama, S.、Honjo, T.、Tashiro, K.：“ESDN，一种新型神经毡蛋白

Stem cell-derived neural stem/progenitor cell supporting factor is an autocrine/paracrine survival factor for adult neural stem/progenitor cells

• DOI: 10.1074/jbc.m305342200
• 发表时间: 2003-09-12
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Toda, H;Tsuji, M;Tashiro, K
• 通讯作者: Tashiro, K

Shinohara, M.T., Ogura, A., Ikegawa, M., Inoue, K., Ogonuki, N., Tashiro K., Toyokuni, S., Honjo, T., Shinohara., T.: "Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice"Proc. Natl. Acad. Sci. U.S.A

Shinohara，M.T.，Ogura，A.，Ikekawa，M.，Inoue，K.，Ogonuki，N.，Tashiro K.，Toyokuni，S.，Honjo，T.，Shinohara.，T.：“腺病毒介导的基因传递

ヒトおよび哺乳動物の幹細胞由来神経生存因子

人类和哺乳动物干细胞衍生的神经存活因子

• 发表时间: 2002