Abramson S, Miller R G, Phillips R A
J Exp Med. 1977 Jun 1;145(6):1567-79. doi: 10.1084/jem.145.6.1567.
The precise relationship between the stem cells for the lymphoid system and those for the blood-forming system is unclear. While it is generally assumed that the hemopoietic stem cell, the spleen colony-forming unit (CFU-S), is also the stem cell for the lymphoid system, there is little evidence for this hypothesis. To investigate the stem cells in these two systems, we irradiated bone marrow cells to induce unique chromosome aberrations in the stem cell population and injected them at limiting dilution into stem cell-deficient recipients. Several months (between 3 and 11) were allowed for the injected cells to repopulate the hemopoietic system. At that time, the bone marrow, spleen, and thymus were examined for a high frequency of cells having the same unique chromosome aberration. The presence of such markers shows that the marker was induced in a cell with extensive proliferative capacity, i.e., a stem cell. In addition, the splenic lymphocytes were stimulated with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) to search for unique chromosomes in dividing T and B cells, respectively. Finally, bone marrow cells were injected into secondary irradiated recipients to determine if the marker occurred in CFU-S and to determine whether or not the same tissue distributions of marked cells could be propogated by bone marrow cells in a second recipient. After examination of 28 primary recipients, it was possible to identify three unique patterns of stem cell regeneration. In one set of mice, a unique chromosome marker was observed in CFU-S and in PHA- and LPS-stimulated cultures. These mice provide direct evidence for a pluripotent stem cell in bone marrow. In addition, two restricted stem cells were identified by this analysis. In three recipients, abnormal karyotypes were found only in myeloid cells and not in B and T lymphocytes. These mice presumably received a marked stem cell restricted to differentiate only into myeloid progeny. In three other recipients, chromosome aberrations were found only in PHA-stimulated cells; CFU-S and cells from LPS cultures did not have cells with the unique chromosome. This pattern suggests that bone marrow contains cells committed to differentiation only into T lymphocytes. For each of the three types of stem cells, secondary recipients had the same cellular distribution of marked cells as the primary recipients. This observation provides further evidence that unique markers can be induced in both pluripotent and restricted stem cells.
淋巴系统干细胞与造血系统干细胞之间的确切关系尚不清楚。虽然一般认为造血干细胞，即脾集落形成单位（CFU-S），也是淋巴系统的干细胞，但这一假设几乎没有证据支持。为了研究这两个系统中的干细胞，我们对骨髓细胞进行照射，以在干细胞群体中诱导独特的染色体畸变，并将它们以极限稀释的方式注入干细胞缺陷的受体中。让注入的细胞有几个月（3到11个月）的时间来重新填充造血系统。此时，对骨髓、脾脏和胸腺进行检查，寻找具有相同独特染色体畸变的高频细胞。这些标记物的存在表明该标记物是在具有广泛增殖能力的细胞，即干细胞中诱导产生的。此外，分别用植物血凝素（PHA）或脂多糖（LPS）刺激脾淋巴细胞，以在分裂的T细胞和B细胞中寻找独特的染色体。最后，将骨髓细胞注入二次照射的受体中，以确定标记物是否出现在CFU-S中，并确定标记细胞的相同组织分布是否能由骨髓细胞在第二个受体中传播。在检查了28只初级受体后，有可能识别出三种独特的干细胞再生模式。在一组小鼠中，在CFU-S以及PHA和LPS刺激的培养物中观察到独特的染色体标记物。这些小鼠为骨髓中存在多能干细胞提供了直接证据。此外，通过该分析还鉴定出了两种受限干细胞。在三只受体中，仅在髓细胞中发现异常核型，而在B细胞和T淋巴细胞中未发现。这些小鼠可能接受了一种仅限于分化为髓系后代的标记干细胞。在另外三只受体中，仅在PHA刺激的细胞中发现染色体畸变；CFU-S和LPS培养物中的细胞没有具有独特染色体的细胞。这种模式表明骨髓中含有仅致力于分化为T淋巴细胞的细胞。对于这三种类型的干细胞中的每一种，二次受体中标记细胞的细胞分布与初级受体相同。这一观察结果进一步证明，在多能和受限干细胞中都可以诱导出独特的标记物。
