CD27:CD70 signaling in hematopoietic stem cell formation

CD27:CD70 信号在造血干细胞形成中的作用

• 批准号: 9374787
• 负责人: NANCY SPECK
• 金额: $ 20.78万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-26 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9374787
• 关键词: Adult; Alpha Cell; Anatomy; Antigen-Presenting Cells; Arteries; B-Lymphocytes; Blood Cells; Bone Marrow; CD70 antigen; Cell Count; Cell Differentiation process; Cell Lineage; Cell Surface Receptors; Cell surface; Cells; Confocal Microscopy; Data; Dendritic Cells; Embryo; Embryonic Development; Endothelial Cells; Endothelium; Family; Goals; Hematopoietic; Hematopoietic stem cells; Immune; Inflammation; Inflammatory; Lymphocyte; MAPK8 gene; Marrow; Measures; Molecular Profiling; Mus; Natural Killer Cells; Pathway interactions; Reagent; Regenerative Medicine; Research; Signal Pathway; Signal Transduction; Source; T-Cell Activation; T-Lymphocyte; Testing; Transplantation; Tumor Necrosis Factor Receptor; base; cell type; member; progenitor; transcriptome sequencing

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.

概括 该建议的目的是了解肿瘤坏死因子成员CD27的信号是否发出信号 受体超家族，调节胚胎中的造血干细胞形成。了解HSC 形式，尤其是胚胎HSC形成所涉及的信号传导途径将是必不可少的 用于从其他细胞来源产生和扩展HSC，这是再生的主要目标 药品。所有成年HSC均源自胚胎中的血液生成内皮细胞。血液内皮 位于几个解剖部位，但仅主要动脉中的血肿内皮会产生HSC和 HSC的未成熟前体称为前HSC。我们和其他人发现多种先天免疫和 炎症信号通路调节主要动脉中的HSC形成。我们还确定了一个单元 表面受体CD27，在前HSC和HSC上表达。在成年人中，CD27激活炎症 通过NF-κB和JNK途径传导。我们将测试CD27信号传导调节NF-的假设 κB信号传导以及胚胎中HSC和HSC的数量。我们还将确定 表达CD70的细胞，CD27的配体。