Tissue homogeneity requires inhibition of unequal gene silencing during development.
Tissue homogeneity requires inhibition of unequal gene silencing during development.
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DOI：
10.1083/jcb.201601050
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发表时间：
2016-08-01
期刊：
影响因子：
--
通讯作者：
Jose AM
中科院分区：
文献类型：
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作者：
Le HH;Looney M;Strauss B;Bloodgood M;Jose AM
同质的细胞群构成了个体组织，然而生物体是如何实现这种同质性的尚不清楚。Le等人利用秀丽隐杆线虫的肠道揭示了RNA沉默的启动物在细胞间的分离不均匀。在早期发育过程中抑制这种不平等可以实现组织均匀性。多细胞生物可以产生并维持构成单个组织的同质细胞群。然而，可以破坏同质性的细胞过程以及生物体如何克服这种破坏是未知的。我们发现，秀丽隐杆线虫肠道细胞之间的重复DNA转基因表达差异可达100倍。这些差异是由某些细胞中的基因沉默引起的，并受到亲代和合子因子（如保守的外切酶ERI-1）的积极抑制。如果不受抑制，沉默可以在胚胎中的一些细胞之间传播，但可能是重复特异性的，并且独立于每个细胞内的其他同源位点。沉默可以通过DNA复制和核分裂持续存在，破坏发达动物的均匀基因表达。单细胞分辨率分析表明，细胞之间的差异出现在细胞分裂早期，由于沉默启动子的不平等分离。我们的研究结果表明，具有高重复DNA含量的生物体，包括人类，可以使用类似的发育机制来实现和维持组织的同质性。
Homogenous populations of cells make up individual tissues, yet how organisms achieve such homogeneity is unknown. Le et al. use the C. elegans intestine to reveal that an initiator of RNA silencing is segregated unequally between cells. Suppression of this inequality during early development achieves tissue homogeneity. Multicellular organisms can generate and maintain homogenous populations of cells that make up individual tissues. However, cellular processes that can disrupt homogeneity and how organisms overcome such disruption are unknown. We found that ∼100-fold differences in expression from a repetitive DNA transgene can occur between intestinal cells in Caenorhabditis elegans. These differences are caused by gene silencing in some cells and are actively suppressed by parental and zygotic factors such as the conserved exonuclease ERI-1. If unsuppressed, silencing can spread between some cells in embryos but can be repeat specific and independent of other homologous loci within each cell. Silencing can persist through DNA replication and nuclear divisions, disrupting uniform gene expression in developed animals. Analysis at single-cell resolution suggests that differences between cells arise during early cell divisions upon unequal segregation of an initiator of silencing. Our results suggest that organisms with high repetitive DNA content, which include humans, could use similar developmental mechanisms to achieve and maintain tissue homogeneity.