Vainchenker W, Debili N, Methia N, Mouthon M A, Wendling F
INSERM U. 362, Institut Gustave Roussy, Villejuif.
Bull Acad Natl Med. 1994 May;178(5):753-78; discussion 778-9.
Hematopoiesis is the cellular system which leads to the continuous production of blood cells. This highly complex cellular system is organized into three main compartments: (i) stem cells which are both pluripotent and theoretically capable of self renewal; (ii) hematopoietic progenitors which are committed to (only) one cell lineage and are able to proliferate along each particular differentiation pathway; (iii) a maturation compartment in which cells become morphologically identifiable since they synthesize lineage specific proteins. The maturation cell compartment represents the majority of marrow cells. At the present time, the regulation of true stem cells remains poorly understood since these cells are difficult to assay in vitro. In contrast, the regulation of each hematopoietic lineages becomes to be well known. These knowledges are mainly due to two reasons: (i) hematopoietic progenitors can be purified and assayed in culture. Their proliferation and differentiation are strictly dependent upon the presence of hematopoietic growth factors; (ii) these different hematopoietic growth factors have been isolated and their cDNA cloned. Erythropoiesis and megakaryocytopoiesis are two branches of hematopoiesis which lead to the production of RBC and platelets, respectively. These two cell lineages have several common features. However, they markedly differ by their regulation since RBC production depends upon one main stimulus (hypoxia) and, therefore, the terminal erythroid differentiation is regulated by a single growth factor. In contrast, regulation of platelet production may depend on several stimuli such as the platelet mass (homeostasis), inflammation, infection and hypoxia. Therefore, several cytokines are involved in the regulation of megakaryocytopoiesis. In addition, the mechanisms of platelet production are highly complex and, in contrast to all the other hematopoietic lineages where the production of mature cells depends on a single parameter (the proliferation during differentiation), three independent parameters modify thrombopoiesis: a) the number of marrow megakaryocytes (MK) (proliferation of the precursor cells). b) the megakaryocyte volume which directly depends on the MK ploidy. During MK differentiation, MK precursors switch from a mitotic process (DNA duplication followed by cytokinesis) to an endomitotic process (DNA duplication without cytokinesis). Endomitosis is a specific process of the megakaryocytic differentiation and differs from all the other cellular models of polyploidization by the existence of a single polyploid and polylobulated nucleus in each cell. This polyploidization induces a major amplification of the platelet production since it is associated with a parallel increase in the cytoplasmic mass.(ABSTRACT TRUNCATED AT 400 WORDS)
造血作用是导致血细胞持续生成的细胞系统。这个高度复杂的细胞系统被组织成三个主要部分:(i)干细胞,它们具有多能性且理论上能够自我更新;(ii)造血祖细胞,它们仅定向分化为一种细胞谱系,并且能够沿着每个特定的分化途径增殖;(iii)成熟部分,在这个部分细胞由于合成谱系特异性蛋白质而在形态上变得可识别。成熟细胞部分代表了骨髓细胞的大部分。目前,真正干细胞的调节仍知之甚少,因为这些细胞在体外难以检测。相比之下,每个造血谱系的调节已为人熟知。这些知识主要归因于两个原因:(i)造血祖细胞可以在培养中被纯化和检测。它们的增殖和分化严格依赖于造血生长因子的存在;(ii)这些不同的造血生长因子已被分离,并且它们的cDNA已被克隆。红细胞生成和巨核细胞生成是造血作用的两个分支,分别导致红细胞和血小板的产生。这两个细胞谱系有几个共同特征。然而,它们在调节方面有显著差异,因为红细胞生成依赖于一个主要刺激(缺氧),因此,终末红细胞分化由单一生长因子调节。相比之下,血小板生成的调节可能依赖于多种刺激,如血小板数量(内稳态)、炎症、感染和缺氧。因此,几种细胞因子参与巨核细胞生成的调节。此外,血小板生成的机制高度复杂,与所有其他造血谱系不同,在其他造血谱系中成熟细胞的产生依赖于一个单一参数(分化过程中的增殖),而血小板生成由三个独立参数调节:a)骨髓巨核细胞(MK)的数量(前体细胞的增殖)。b)巨核细胞体积,它直接取决于MK的倍性。在MK分化过程中,MK前体细胞从有丝分裂过程(DNA复制后接着胞质分裂)转变为核内有丝分裂过程(DNA复制但无胞质分裂)。核内有丝分裂是巨核细胞分化的一个特定过程,与所有其他多倍体化的细胞模型不同,每个细胞中存在单个多倍体且分叶的细胞核。这种多倍体化导致血小板生成的主要扩增,因为它与细胞质质量的平行增加相关。(摘要截取自400字)