Primordial cell pool size and lineage relationships of five human cell types*
Primordial cell pool size and lineage relationships of five human cell types*
复制标题
五种人类细胞类型的原始细胞库大小和谱系关系*
作者：
P. Fialkow
可以在具有两种或多种遗传上不同类型的细胞的个体中研究正常和肿瘤发育的几个方面。X-连锁葡萄糖-6-磷酸脱氢酶（G-6-PD）基因座杂合的雌性动物是细胞嵌合体，这是由于胚胎发生早期每个体细胞中一条X染色体的固定失活（里昂，1968）。因此，GdBIGdA杂合子中的给定体细胞具有GdB或GdA活性（Beutler，Yeh &费尔班克斯，1962; Davidson，Nitowsky &查尔兹，1963; DeMars & Nance，1964）。通过将相应的酶进行淀粉凝胶电泳，可以将来自具有活性GdA等位基因的细胞的克隆与其中GdB是活性的那些克隆区分开，A型酶比B酶迁移更快。因此，G-6-PD杂合子有两个细胞群，每个细胞群都被其产生的酶类型标记或标记。自Linder和Gartler（1965）首次报道以来，该系统已被广泛用于追踪人类肿瘤的起源和发展（Fialkow，1972年综述）。在GdB/GdA杂合子中具有克隆起源的肿瘤应仅含有B型或A型酶（取决于GdB或GdA在单个祖细胞中是否具有活性）;具有多细胞起源的肿瘤可能含有A和B型酶。同样，G-6-PD方法也可用于追踪正常发育。一种应用是比较来自许多受试者的相同器官中A酶与B酶的比率。由于酶的组成反映了镶嵌细胞的组成，通过某些假设，可以估计在胚胎发生过程中有多少细胞产生了该器官。如果它是在X失活发生后从单个细胞衍生的，那么应该只发现一种类型的酶，A或B。如果有两个祖细胞，那么来自114个杂合子的器官应该分型为A，112个a，s AB，114个为B，等等。如果原始细胞的数量很大，来自几乎0.11 GdB/GdA雌性的器官应该含有大约等量的A和B酶。另一个应用研究的许多不同的组织从一个单一的主题提供了有关细胞谱系关系的信息。如果两个组织来自同一个祖先库，它们应该在两种同工酶的比率上显示出相关性。例如，Gandini和Gartler（1969）发现红细胞、粒细胞和血液淋巴细胞中A酶与B酶的比率之间存在极好的相关性，并得出结论，这些细胞系来源于共同的干细胞库。在先前的报告中，仅在两名患者中比较了血细胞的镶嵌组成与皮肤的镶嵌组成（Gandini等人，1968）。我们研究了42个GdB/GdA杂合子的红细胞、粒细胞、血淋巴细胞、淋巴结、皮肤和肌肉五种细胞类型。
Several aspects of normal and neoplastic development can be studied in individuals who have two or more genetically distinct types of cells. Females heterozygous at the X-linked glucose-6phosphate dehydrogenase (G-6-PD) locus are cellular mosaics by virtue of fixed inactivation of one X chromosome in each somatic cell early in embryogenesis (Lyon, 1968). Thus, a given somatic cell in a GdBIGdA heterozygote has either GdB or GdA active (Beutler, Yeh & Fairbanks, 1962; Davidson, Nitowsky & Childs, 1963; DeMars & Nance, 1964). Clones derived from cells with an active GdA allele can be distinguished from those in which GdB is active by subjecting the respective enzymes to starch-gel electrophoresis the A type migrates more rapidly than the B enzyme. Therefore G-6-PD heterozygotes have two cell populations each of which is marked or tagged by the type of enzyme it produces. Since the first report by Linder & Gartler (1965) this system has been used extensively to trace the origin and development of human neoplasms (reviewed in Fialkow, 1972). A tumour with a clonal origin in a GdB/GdA heterozygote should contain only type B or type A enzyme (depending upon whether GdB or GdA was active in the single progenitor cell) ; a tumour with multicellular origin may contain both A and B enzymes. Similarly, the G-6-PD method can also be used to trace normal development. One application is to compare the ratio of A to B enzyme in the same organ from many subjects. Since the enzyme composition reflects the mosaic cell composition, with certain assumptions estimates can then be made of how many cells gave rise to that organ during embryogenesis. If it were derived from a single cell after X inactivation has occurred, only one type of enzyme, A or B, should be found. If there were two progenitor cells, the organs from 114 of heterozygotes should type as A, 112 a,s AB, and 114 as B, and so on. If the number of primordial cells is large, the organ from almost a.11 GdB/GdA females should contain approximately equal amounts of A and B enzyme. Another application study of many different tissues from a single subject provides information about cell lineage relationships. If two tissues are derived from a common progenitor pool they should show correlations in the ratio of the two isoenzymes. For example, Gandini & Gartler (1969) found excellent correlations among the ratios of A to B enzymes in red cells, granulocytes and blood lymphocytes and concluded that these cell lines are derived from a common stem cell pool. In previous reports the mosaic compositions of blood cells have been compared with that of skin in only two patients (Gandini et al. 1968). We have studied five human cell types red cells, granulocytes, blood lymphocytes, lymph nodes, skin a.nd muscle from 42 GdB/GdA heterozygotes.