THE STUDY OF HUMAN ERYTHROPOIESIS

一些疾病的治疗，包括血红蛋白病和 疟疾需要对人类有一个基本的了解 红血球生成。许多实验方法旨在理解 这个过程本身就是有缺陷的，因为它们涉及非人类细胞或 从转化的细胞衍生的细胞系。红细胞生成的研究进展 在初级红细胞中的作用受到实验缺陷的阻碍 与这些细胞的体外培养有关。我们已经采取了一项 早期前瞻性研究的直接方法 包括人类红血球生成的转录事件。使用流 流式细胞术分析正常志愿者的液体培养血液 已经鉴定并在时间上对红系连续体进行了表型鉴定 这些大规模培养物中存在的细胞。这种方法导致了 鉴定转录上与之结合的红细胞 红系分化。令人惊讶的是，在这些人口中 细胞能够在半固体介质中形成巨大的集落 在正常情况下，分化和增殖并不总是耦合的 人类的造血功能。最不成熟的造血者 致力于转录红系特异的 基因代表着一种研究细胞增殖和增殖的卵黄细胞 与正常和异常人类相关的分化事件 红血球生成。我们近期的目标是描述 这些细胞通过抗原性和进一步的转录表型鉴定。一次 与正常红细胞生成相关的转录事件有 定义、关联，旨在了解涉及红色的疾病状态 血细胞可能是可能的。

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.