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.

总结 该提案的目标是了解来自肿瘤坏死因子成员CD 27的信号传导是否 受体超家族，调节胚胎中造血干细胞的形成。了解HSC如何 形式，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离体产生和扩增HSC，这是再生造血干细胞的主要目标。 药所有成体HSC均来源于胚胎中的生血内皮细胞。造血内皮 位于几个解剖部位，但只有大动脉中的生血内皮细胞产生HSC， 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 炎症信号传导途径调节主要动脉中HSC的形成。我们还发现了一个 表面受体CD 27在前HSC和HSC上表达。在成人中，CD 27激活炎症性 通过NF-κB和JNK途径进行信号传导。我们将检验CD 27信号调节NF-κ B的假设。 κB信号和胚胎中前HSC和HSC的数量。我们还将确定 表达CD 27配体CD 70的细胞。