THE STUDY OF HUMAN ERYTHROPOIESIS

人类红细胞生成的研究

• 批准号: 6161922
• 负责人: J L MILLER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161922
• 关键词: cell differentiation; cell proliferation; differentiation antigens; erythroid stem cell; erythropoiesis; flow cytometry; genetic transcription; human tissue; mass tissue /cell culture; phenotype

The treatment of a number of diseases including hemoglobinopathies and malaria will require a fundamental understanding of human erythropoiesis. Many experimental methodologies aimed at understanding this process are inherently flawed as they involve nonhuman cells or cell lines derived from transformed cells. The study of erythropoiesis in primary erythroblasts has been handicapped by experimental pitfalls associated with the ex vivo culture of those cells. We have taken a direct approach toward the prospective study of the early transcriptional events that encompass human erythropoiesis. Using flow cytometry to analyze liquid cultured blood from normal volunteers, we have identified and temporally phenotyped the erythroid continuum of cells present in these mass cultures. This approach has led to the identification of erythroblasts that are transcriptionally committed to erythroid differentiation. Surprisingly, within that population are cells able to form giant colonies in semisolid media suggesting differentiation and proliferation are not invariably coupled in normal human hematopoiesis. The most immature hematopoietic that have committed themselves toward the transcription of erythroid-specific genes represent a pivitol cell for the study of proliferation and differentiation events associated with normal and abnormal human erythropoiesis. Our immediate future goal is the characterization of these cells by antigenic and further transcriptional phenotyping. Once the transcriptional events associated with normal erythropoiesis are defined, correlates aimed at understanding disease states involving red blood cells may be possible.

治疗多种疾病，包括血红蛋白病和 疟疾将需要对人类 红细胞生成 许多实验方法旨在了解 这一过程存在固有的缺陷，因为它们涉及非人类细胞， 来源于转化细胞的细胞系。 红细胞生成的研究 在初级成红细胞中的应用受到实验缺陷的阻碍 与这些细胞的离体培养相关。我们采取了一 对早期的前瞻性研究的直接方法 包括人类红细胞生成的转录事件。 使用流式 流式细胞术分析正常志愿者的液体培养血液，我们 已经确定并暂时分型了红细胞连续体， 这些大量培养物中存在的细胞。 这种做法导致了 鉴定转录定型的成红细胞 红系分化 令人惊讶的是，在这些人群中， 细胞能够在半固体培养基中形成巨大的集落， 分化和增殖在正常细胞中并不总是偶联的。 人类造血 最不成熟的造血系统 致力于转录红细胞特异性 基因代表用于研究增殖的pivitol细胞， 与正常和异常人类相关的分化事件 红细胞生成 我们近期的目标是描述 这些细胞的抗原和进一步的转录表型。 一旦 与正常红细胞生成相关的转录事件是 定义，旨在了解涉及红色的疾病状态的相关性 血细胞是可能的。