What keeps cells in tissues behaving normally in the face of myriad mutations?
What keeps cells in tissues behaving normally in the face of myriad mutations?
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DOI：
10.1002/bies.20403
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发表时间：
2006-05-01
期刊：
影响因子：
4
通讯作者：
Rubin, H
中科院分区：
文献类型：
--
作者：
Rubin, H
在转基因小鼠中使用报告基因表明，每个体细胞中有许多局部突变和大的基因组重排，这些突变和重排随着年龄的增长以不同的速率在每个器官中积累，但没有明显的影响。分离细胞进行单层培养会导致细胞之间大小的巨大异质性和功能的丧失，这可能反映了细胞之间的遗传和表观遗传差异，但在组织中被掩盖。大量相邻的正常细胞的调节能力表现为使孤立的嗜同性肿瘤细胞的外观和生长行为正常化，并重新定向孤立的嗜异性干细胞样细胞的分化。需要相互作用的细胞之间的密切接触来诱导这些变化。肿瘤表型的正常化不需要细胞间的间隙连接通信，尽管转分化可能需要。这些不同的关系是“大的有秩序而小的不均匀”这一统一的生物学原理的表现。生物学报，2006,28(5):515-524。(c) 2006 Wiley期刊公司
The use of a reporter gene in transgenic mice indicates that there are many local mutations and large genomic rearrangements per somatic cell that accumulate with age at different rates per organ and without visible effects. Dissociation of the cells for monolayer culture brings out great heterogeneity of size and loss of function among cells that presumably reflect genetic and epigenetic differences among the cells, but are masked in organized tissue. The regulatory power of a mass of contiguous normal cells is expressed in its capacity to normalize the appearance and growth behavior of solitary homophilic neoplastic cells, and to redirect differentiation of solitary heterophilic stem-like cells. Intimate contact between the interacting cells is required to induce these changes. The normalization of the neoplastic phenotype does not require gap junctional communication between cells, though transdifferentiation might. These varied relationships are manifestations of the unifying biological principle of "order in the large over heterogeneity in the small". BioEssays 28:515-524, 2006. (c) 2006 Wiley Periodicals, Inc.