Mintz B, Anthony K, Litwin S
Proc Natl Acad Sci U S A. 1984 Dec;81(24):7835-9. doi: 10.1073/pnas.81.24.7835.
Mutant mouse fetuses with a hematopoietic stem cell defect were injected with a mixture of two normal strains of fetal liver cells to test the possibility of seeding with single stem cells and of deriving all hematopoietic lineages clonally. Recipients were either Wf/Wf, with a mild endogenous defect offering only marginal selective advantage to a normal donor cell, or W/W, with a severe defect. Among 11 Wf/Wf animals with long-term grafts, 8 had only one or the other of the donor strains. Some of these individuals must have been seeded by only a single donor cell (P = 0.1); the frequency of this event was at least 20% (90% confidence) and most likely 50% of the cases. Cell-specific strain markers in myeloid and lymphoid lineages reinforced the likelihood that renewal and differentiation had occurred from a totipotent hematopoietic stem cell. In a smaller W/W group, some hosts were seeded by at most two cells (P = 0.1), and single-cell seeding could not be ruled out. The experiment allows stem cell pedigrees to be examined during the normal developmental progression. In both groups observed here, some mice displayed a regular and complementary rise and fall in proportions of cells of different genotypes, thereby suggesting clonal succession in a hierarchy of stem cell compartments. This transplant system also offers advantages for future experiments on regulated expression in vivo of genes transferred (in vitro) into totipotent hematopoietic stem cells.
将具有造血干细胞缺陷的突变小鼠胎儿注射两种正常品系的胎儿肝细胞混合物，以测试单个干细胞播种以及克隆衍生所有造血谱系的可能性。受体要么是Wf/Wf，其具有轻度内源性缺陷，对正常供体细胞仅提供微弱的选择优势；要么是W/W，其具有严重缺陷。在11只具有长期移植的Wf/Wf动物中，8只仅含有一种或另一种供体品系。这些个体中的一些肯定仅由单个供体细胞播种（P = 0.1）；该事件的频率至少为20%（90%置信度），很可能在50%的病例中发生。髓系和淋巴系中的细胞特异性品系标记增强了从全能造血干细胞发生更新和分化的可能性。在一个较小的W/W组中，一些宿主最多由两个细胞播种（P = 0.1），并且不能排除单细胞播种。该实验允许在正常发育进程中检查干细胞谱系。在此处观察的两组中，一些小鼠不同基因型细胞的比例呈现出规则且互补的升降，从而表明在干细胞区室层次结构中存在克隆演替。这种移植系统也为未来关于（体外）转入全能造血干细胞的基因在体内的调控表达实验提供了优势。
