CD27:CD70 signaling in hematopoietic stem cell formation

摘要 这项提议的目标是了解来自肿瘤坏死因子成员CD27的信号 受体超家族，调节胚胎中造血干细胞的形成。了解HSC如何 形成，特别是参与胚胎HSC形成的信号通路将是必不可少的 用于从其他细胞来源体外培养和扩增HSCs，这是再生的一个主要目标 医药。所有成年的造血干细胞都来自胚胎中的血源性内皮细胞。血源性内皮 分布在几个解剖部位，但只有主要动脉中的血源性内皮细胞产生HSCs和 未成熟的HSCs前体称为前HSCs。我们和其他人发现，多重先天免疫和 炎症信号通路调节主动脉HSC的形成。我们还确认了一个细胞 表面受体CD27表达于前HSCs和HSCs。在成人中，CD27激活炎症 通过核因子-κB和JNK通路进行信号传递。我们将检验CD27信号调节核因子的假说。 κB信号和胚胎中前-HSCs和HSCs的数量。我们还将确定 表达CD27的配体CD70的细胞。

Summary The goal of this proposal is to understand whether signaling from CD27, a member of the tumor necrosis factor receptor superfamily, regulates hematopoietic stem cell formation in the embryo. Understanding how HSCs form, and in particular the signaling pathways that are involved in embryonic HSC formation will be essential for producing and expanding HSCs from other cell sources ex vivo, which is a major goal in regenerative medicine. All adult HSCs are derived from hemogenic endothelial cells in the embryo. Hemogenic endothelium is located in several anatomic sites, but only hemogenic endothelium in the major arteries produces HSCs and immature precursors of HSCs called pre-HSCs. We and others discovered that multiple innate immune and inflammatory signaling pathways regulate HSC formation in the major arteries. We have also identified a cell surface receptor, CD27, expressed on pre-HSCs and HSCs. In the adult, CD27 activates inflammatory signaling through the NF-κB and JNK pathways. We will test the hypothesis that CD27 signaling regulates NF- κB signaling and the number of pre-HSCs and HSCs in the embryo. We will also determine the identity of the cells expressing CD70, the ligand for CD27.