Klar A J
Cold Spring Harbor Laboratory, NY 11724.
EMBO J. 1990 May;9(5):1407-15. doi: 10.1002/j.1460-2075.1990.tb08256.x.
A key feature for development consists of producing sister cells that differ in their potential for cellular differentiation. Following two cell divisions, a haploid Schizosaccharomyces pombe cell produces one cell in four 'granddaughters' with a changed mating cell type, implying nonequivalence of sister cells in each of two consecutive cell divisions. The observed pattern of switching is analogous to the mammalian 'stem cell' lineage by which a cell produces one daughter like itself while the other daughter is advanced in its developmental program. It is tested here whether sisters differ because of unequal distribution of cytoplasmic and/or nuclear components to them or due to inheriting a specific parental DNA chain at the mating type locus. Only the DNA strand-segregation model predicts that those cells engineered to contain an inverted tandem duplication of the mating type locus should produce equivalent sisters. Consequently, two 'cousins' in four related granddaughter cells should switch. The results verified the prediction, thus establishing that all cells otherwise fully possess the potential to switch. Therefore, the program of cell type change in S.pombe cell lineages is determined by the pattern of DNA strand inheritance at the mating type locus. A specific DNA sequence present at the mating type locus is postulated to be the cause of developmental asymmetry between sister cells. A general model for cellular differentiation is proposed in which the act of DNA replication itself is hypothesized to produce developmentally nonequivalent sister genomes.
发育的一个关键特征是产生在细胞分化潜能上存在差异的姐妹细胞。经过两次细胞分裂后，单倍体粟酒裂殖酵母细胞在四个“孙女”细胞中有一个细胞的交配细胞类型发生了变化，这意味着在连续的两次细胞分裂中，每个分裂过程中姐妹细胞都是不等同的。观察到的转换模式类似于哺乳动物的“干细胞”谱系，即一个细胞产生一个与其自身相似的子代细胞，而另一个子代细胞则在其发育程序上更进一步。本文测试了姐妹细胞存在差异是因为细胞质和/或核成分向它们的分配不均，还是由于在交配型位点继承了特定的亲本DNA链。只有DNA链分离模型预测，那些经过基因工程改造以包含交配型位点反向串联重复的细胞应该产生等同的姐妹细胞。因此，在四个相关的孙女细胞中，应该有两个“表亲”发生转换。结果证实了这一预测，从而确定所有细胞在其他方面都完全具有转换的潜力。因此，粟酒裂殖酵母细胞谱系中的细胞类型变化程序是由交配型位点的DNA链遗传模式决定的。推测交配型位点上存在的特定DNA序列是姐妹细胞之间发育不对称的原因。本文提出了一个细胞分化的通用模型，其中假设DNA复制行为本身会产生发育上不等同的姐妹基因组。
