HEMOPOIETIC STEM CELL DIFFERENTIATION TO MACROPHAGES

造血干细胞分化为巨噬细胞

• 批准号: 3170435
• 负责人: E. RICHARD STANLEY
• 金额: $ 34.82万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-02-01 至 1997-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3170435
• 关键词: Caenorhabditis elegans; Drosophilidae; biological signal transduction; cell differentiation; cell growth regulation; cell sorting; colony stimulating factor; cytokine receptors; gene mutation; genes; genetic manipulation; genetically modified animals; growth factor receptors; hematopoietic stem cells; human tissue; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rabbit; laboratory rat; macrophage; molecular cloning; monoclonal antibody; northern blottings; polymerase chain reaction; radioimmunoassay; tissue /cell culture

Mononuclear phagocytic cells comprise bone marrow progenitor cells, blood monocytes and tissue macrophages. The growth factor, colony stimulating factor-1 (CSF-1), humorally regulates mononuclear phagocytes and locally regulates placental function. Interestingly, CSF-1 can be either expressed on the cell surface or rapidly secreted from cells. The overall aim of this project is to study how CSF-1 locally and humorally regulates target cells in the mouse and in lower organisms with highly developed genetics. In the mouse, this aim will be addressed by studying a mouse mutant which totally lacks CSF-1 due to an inactivating mutation in the CSF-1 gene. It is proposed to define those situations in which CSF-1 is acting at a distance and those in which it is acting locally and, if locally, whether this action requires cell-cell contact between CSF-1-producing and CSF-1- responding cells. Experiments will involve attempts to reconstitute the mutant mice by administration of CSF-1 or transgenically, using constructs expressing different forms of CSF-1. Other experiments with this mouse and normal mice will be directed towards understanding the role of CSF-1 in primitive hemopoietic cell production. In addition, it is proposed to clone the genes for the CSF-1R in and its ligand in Drosophila and Caenorhabditis elegans in order to compare and contrast the roles of the receptor and its ligand in these organisms with their roles in mammalian systems, as well as to develop genetic approaches for the analysis of CSF-1 signal transduction pathways and for the regulation of CSF-1 expression.

单核吞噬细胞包含骨髓祖细胞，血液 单核细胞和组织巨噬细胞。 生长因子，菌落刺激 因子1（CSF-1），在幽默地调节单核吞噬细胞和局部 调节胎盘功能。 有趣的是，可以表达CSF-1 在细胞表面或从细胞迅速分泌。 总体目的 该项目是研究CSF-1如何在本地和幽默地调节目标 小鼠中的细胞和具有高度发达遗传学的较低生物体中的细胞。 在鼠标中，将通过研究小鼠突变体来解决这个目标 由于CSF-1基因的灭活突变，完全缺乏CSF-1。 它 提议定义CSF-1在某个情况下作用的情况 距离和当地行动的距离，如果在当地，是否 该动作需要CSF-1产生和CSF-1-之间的细胞细胞接触 响应细胞。 实验将涉及重新建立的尝试 通过使用构建体给予CSF-1或转基因的突变小鼠 表达不同形式的CSF-1。 使用此鼠标进行的其他实验， 普通小鼠将针对了解CSF-1在 原始的血态性细胞产生。 另外，提议 克隆果蝇中CSF-1R的基因及其配体 秀丽隐杆线虫是为了比较和对比 受体及其在这些生物体中具有在哺乳动物中的作用的配体 系统以及开发遗传方法来分析CSF-1 信号转导途径和CSF-1表达的调节。