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2. 发明申请

WO2004078944A3 THROMBIN, SOLUBLE JAGGEDI, AND TRAP AND GROWTH OF STEM CELLS 审中-公开
标题翻译： THROMBIN，SOLUBLE JAGGEDI，和TRAP和STEM细胞的生长
公开(公告)号：WO2004078944A3
公开(公告)日：2005-05-12
申请号：PCT/US2004006762
申请日：2004-03-05
申请人： MAINE MEDICAL CT RES INST , MACIAG THOMAS , KOLEV VIHREN , VERDI JOSEPH M
发明人： MACIAG THOMAS , KOLEV VIHREN , VERDI JOSEPH M
IPC分类号： C12N5/02 , C12N5/0797 , A61K35/00 , A61K35/14 , A61K35/16 , C12N5/06 , C12N5/10
CPC分类号： C12N5/0623 , C12N2501/42 , C12N2501/998
摘要： The present invention relates to methods based on the interactions of thrombin as a biological regulator. More specifically, the invention relates to the interactions of thrombin with regard to Notch signaling, Jaggedl, PAR1, and cellular effects mediated thereby. The invention relates to the discovery that thrombin cleaves Jagged l to produce non-membrane soluble Jagged l (sJl). The soluble Jagged l protein can affect Notch signaling and, among other things, mediate the release of FGF-1 and/or IL-lalpha from a cell. The invention further relates to the role(s) of thrombin and signaling via Notch proteins and the effect on thrombosis, angiogenesis, and/or differentiation, among other processes. Moreover, the invention relates to discovery that thrombin, sJl, and TRAP mediate, inter alia, rapid non-classical release of FGF-1, and proteins associated therewith (e.g., p40 Synl and S100A13, among others), and the effect growth and proliferation of a stem cell without loss of differentiation potential. Thus, the present invention relates to methods of clonally expanding a pluripotent stem cell while preserving the differentiation potential of the cell, a process termed "stamatogenesis."
摘要翻译：本发明涉及基于凝血酶作为生物调节剂的相互作用的方法。更具体地，本发明涉及凝血酶与Notch信号传导，Jagged1，PAR1以及由此介导的细胞效应的相互作用。本发明涉及凝血酶切割锯齿状I以产生非膜可溶性Jagged l（sJ1）的发现。可溶性Jagged I蛋白可以影响Notch信号传导，并且其中包括从细胞介导FGF-1和/或IL-1α的释放。本发明还涉及凝血酶的作用和通过Notch蛋白的信号通路以及其他过程中对血栓形成，血管生成和/或分化的作用。此外，本发明涉及发现凝血酶，sJ1和TRAP尤其介导FGF-1的快速非经典释放和与其相关的蛋白质（例如，p40 Synl和S100A13等），以及效应生长和干细胞的增殖而不损失分化潜能。因此，本发明涉及克隆扩增多能干细胞同时保持细胞的分化潜能的方法，称为“致死生成”的过程。

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