Harrison D E, Astle C M, Lerner C
Jackson Laboratory, Bar Harbor, ME 04609.
Proc Natl Acad Sci U S A. 1988 Feb;85(3):822-6. doi: 10.1073/pnas.85.3.822.
We estimated numbers of transplantable primitive stem cells (PSCs) and found evidence that the same PSC continuously produced circulating erythrocytes and lymphocytes. These estimations used the binomial formula on data from recipients of identical portions of marrow mixtures containing two distinguishable cell types. Analysis of variance was used to compare repeated tests within each recipient. Values of pi s or pi c, probabilities that two independently sampled cells were descended from the same PSC, were also estimated, as this does not require the unverified condition that all PSCs contribute equally to the differentiated cell population. Several months after transplantation, erythrocytes were descended from only a single PSC per 1-2 X 10(5) marrow cells injected, several times rarer than previously reported. Percentages of erythrocyte and lymphocyte types in each recipient were closely correlated, with r values ranging from 0.86 to 0.94, in groups receiving 2-8 X 10(5) marrow cells; apparently the same precursors repopulated both myeloid and lymphoid lines in each recipient, as expected of true PSCs. Our data did not fit the clonal succession model, which predicts sequential activation of new PSCs and deactivation of old. Between 76 and 154 days, differentiated erythrocyte precursors were probably exhausted, with no evidence for new precursor activation or for further change between 154 and 250 days. The percentage of newly produced erythrocytes (reticulocytes) of each donor type varied little when individual recipients were followed between 165 and 295 days after transplantation, and variances within recipients were similar at marrow doses from 8 to 200 X 10(5) cells, further contradicting models of sequential activation and deactivation of PSC clones. Thus, transplanted PSCs were continually active during much of the recipient's lifespan.
我们估算了可移植原始干细胞（PSC）的数量，并发现有证据表明同一PSC持续产生循环红细胞和淋巴细胞。这些估算使用了二项式公式，数据来自接受含有两种可区分细胞类型的相同部分骨髓混合物的受体。方差分析用于比较每个受体内部的重复测试。还估算了pi s或pi c的值，即两个独立采样的细胞源自同一PSC的概率，因为这不需要所有PSC对分化细胞群体做出同等贡献这一未经证实的条件。移植后几个月，每注射1 - 2×10⁵个骨髓细胞，红细胞仅源自单个PSC，比先前报道的要稀少几倍。在接受2 - 8×10⁵个骨髓细胞的组中，每个受体中红细胞和淋巴细胞类型的百分比密切相关，r值范围为0.86至0.94；显然，与真正的PSC预期一样，每个受体中的髓系和淋巴系由相同的前体细胞重新填充。我们的数据不符合克隆 succession模型，该模型预测新PSC的顺序激活和旧PSC的失活。在76至154天之间，分化的红细胞前体细胞可能耗尽，在154至250天之间没有新前体细胞激活或进一步变化的证据。当在移植后165至295天跟踪个体受体时，每种供体类型新产生的红细胞（网织红细胞）百分比变化不大，并且在骨髓剂量从8至200×10⁵个细胞时受体内部的方差相似，这进一步反驳了PSC克隆顺序激活和失活的模型。因此，移植的PSC在受体的大部分寿命期间持续活跃。
