REGULATION OF ERYTHROPOIESIS

本研究的主要目的是探索细胞的调控。 尤其是对人类的正常和过度的压制 体外红细胞生成。一般的造血调节(即 骨髓生成和血小板生成)将在一般情况下稍后进行评估 红系祖细胞的体外研究阐明了其作用原理。 本研究的具体目的是：1)探索Ia(DR)的作用 和“类DR”)抗原在红系祖细胞调节中，2)检查 中国人红系抑制细胞的性质及其祖细胞的相互作用 以确定造血抑制的程度 基因受限，3)表征红系抑制细胞和 抑制其作用机制；4)丰富外周血 用于抑制细胞的单个核细胞，最终目标是提供 为了研究抑制子-祖细胞的“纯”细胞群体 互动。与造血细胞减少症相关的抑制细胞 也将在这方面使用，并且5)最终利用 通过这些研究获得的信息来检查红细胞的病因学 先天性发育不良(钻石-布莱克凡)贫血及其他 再生障碍性疾病。这项研究在很大程度上依赖于体外克隆分析 多能和单能承诺的造血祖细胞。 物理方法，如免疫花环、抗体和补体介导 裂解、荧光激活细胞分选(FACS)技术和氚 胸腺嘧啶核苷“自杀”将用于选择造血祖细胞和 表面抗原表达和特定细胞周期的抑制细胞 以达到上述目的。《知识》 从这些研究中获得的成果将有助于更好地理解正常 以及异常的造血功能。对红系细胞的认识 表面，红系抑制细胞的作用机制，以及 对红细胞再生障碍性疾病的病理生理学的了解无疑将导致 改善再生障碍性疾病的治疗策略，无论是先天性的 或者是后天收购。

The major objective of this research is to explore the cellular regulation and in particular the normal and excessive suppression of human erythropoiesis in vitro. Regulation of hematopoiesis in general (i.e. myelopoiesis and thrombopoiesis) will be evaluated later after general principles are elucidated by the in vitro study of erythroid progenitors. The specific aims of this study are to 1) explore the role of the Ia (DR and "DR like") antigens in erythroid progenitor regulation, 2) examine the nature of erythroid suppressor cells and their progenitor interactions in order to determine the extent to which hematopoietic suppression is genetically restricted, 3) characterize the erythroid suppressor cell and the mechanism of its suppression, and 4) enrich peripheral blood mononuclear cells for suppressor cells with the ultimate goal of providing "pure" populations of cells in order to study suppressor-progenitor interactions. Suppressor cells associated with hematopoietic cytopenias will also be utilized in this regard, and 5) finally utilize the information gained by these studies to examine the etiology of the red cell aplasia of congenital hypoplastic (Diamond-Blackfan) anemia and other aplastic states. The research relies heavily upon in vitro clonal assays for multipotent and unipotent committed hematopoietic progenitors. Physical methods such as immune rosetting, antibody and complement mediated lysis, fluorescence activated cell sorter (FACS) techniques and tritiated thymidine "suicide" will be used to select hematopoietic progenitors and suppressor cells for surface antigen expression and specific cell cycle kinetics in order to achieve the aims described above. The knowledge gained from these studies will lead to an improved understanding of normal and abnormal hematopoiesis. The understanding of the erythroid cell surface, the mechanism of action of erythroid suppressor cells, and knowledge of the pathophysiology of red cell aplasia will no doubt lead to improved strategies for the treatment of aplastic states, either congenital or acquired.