Zeuthen J
Humangenetik. 1975;27(4):275-301. doi: 10.1007/BF00278421.
Cytological and chemical analysis of heterokaryons, the immediate product of cell fusion, offer new possibilities for studying the factors responsible for genetic regulation in eukaryotic cells. In comparison with proliferating cell hybrids the heterokaryon state offers the important advantage that a heterokaryon contains two complete genomes since chromosome loss does not occur, but since segregation and recombination are absent, heterokaryons cannot be used for gene mapping in the same way as proliferating cell hybrids. However, if two cell types carrying different genetic defects are fused the analysis can be used for studies of gene complementation. The biological information obtained with heterokaryons has emphasized the role of the cytoplasm in the control of nuclear activity. When a G1 nucleus is brought into contact with the cytoplasm of an S phase cell the G1 nucleus is stimulated to synthesize DNA. If the nucleus is brought into a mitotic cell, the chromatin of the G1 nucleus is forced to condense into prematurely condensed chromosomes. Inactive nuclei such as the dormant chick erythrocyte nucleus will be stimulated to initiate RNA and DNA synthesis when brought into contact with an active cytoplasm by cell fusion. Specific nuclear proteins have been shown to be responsible for this process of reactivation. Other inactive nuclei such as the nuclei of macrophages and spermatozoa have likewise been shown to be reactivated by fusion with active cells. The degree of activation in all of these cases appears to be determined by the state of the active cell. Inactive nuclei are activated to the same level as the active nucleus but seldom beyond this level. If differentiated cells are fused with undifferentiated cells, usually the differentiated character is lost rapidly after fusion. This observation is in agreement with several studies on proliferating cell hybrids indicating some type of negative control of differentiated properties. In heterokaryons obtained by fusion of cells of a similar type of histotypic differentiation usually coexpression of the differentiated markers is observed.
细胞融合的直接产物——异核体的细胞学和化学分析，为研究真核细胞中负责遗传调控的因素提供了新的可能性。与增殖性细胞杂种相比，异核体状态具有重要优势，即异核体包含两个完整的基因组，因为不会发生染色体丢失，但由于不存在分离和重组，异核体不能像增殖性细胞杂种那样用于基因定位。然而，如果将携带不同遗传缺陷的两种细胞类型融合，该分析可用于基因互补研究。通过异核体获得的生物学信息强调了细胞质在控制核活性中的作用。当一个G1期细胞核与一个S期细胞的细胞质接触时，G1期细胞核会被刺激合成DNA。如果将该细胞核引入有丝分裂细胞中，G1期细胞核的染色质会被迫浓缩成早熟凝集染色体。当通过细胞融合与活跃的细胞质接触时，诸如休眠鸡红细胞核等无活性核会被刺激启动RNA和DNA合成。已证明特定的核蛋白负责这种重新激活过程。其他无活性核，如巨噬细胞核和精子核，同样已被证明通过与活跃细胞融合而被重新激活。在所有这些情况下，激活程度似乎由活跃细胞的状态决定。无活性核被激活到与活跃核相同的水平，但很少超过这个水平。如果分化细胞与未分化细胞融合，通常在融合后分化特征会迅速丧失。这一观察结果与关于增殖性细胞杂种的多项研究一致，表明存在某种对分化特性的负调控。在通过相似组织型分化的细胞融合获得的异核体中，通常会观察到分化标志物的共表达。
