胎盘滋养细胞发育过程中的基因组修饰

T. Zybina
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引用次数: 5

摘要

胎盘滋养层细胞提供了一个深刻的基因组修饰的例子,导致全基因组增殖,非整倍性,一些基因或其簇的复制不足,以及相反,基因扩增。这些事件包括在功能不同的细胞系分化程序中。在某些情况下,滋养细胞分化包括通过非有丝分裂实现的去多倍体化。非整倍性也可以由无脊椎动物和植物不寻常的有丝分裂特征来解释;在哺乳动物中,它可能是由着丝粒染色体区域的低甲基化引起的。巨型(内多倍体)滋养细胞组织包括“松散核小体”,由非规范组蛋白变体,即H2AX, H2AZ和H3组成。3.与小鼠TGC一样,侵入子宫内膜的人上皮外滋养细胞中,与非侵入性滋养细胞群体相比,甲基化发生了显著变化。与此同时,一些基因在滋养细胞谱系分化开始时出现了高甲基化。因此,尽管染色体可视化的可能性有限,但滋养细胞代表了一个有趣的模型来研究基因拷贝数的修饰及其表达对正常或异常细胞分化的重要作用。
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Genome Modifications Involved in Developmental Programs of the Placental Trophoblast
The placental trophoblast cells give an example of profound genome modifications that lead to whole-genome multiplication, aneuploidy, under-replication of some genes or their clusters as well as, by contrast, gene amplification. These events are included into program of differentiation of functionally different cell lineages. In some cases the trophoblast cell differentiation involves depolyploidization achieved by non-mitotic division. Aneuploidy may be also accounted for by the unusual mitoses characteristic of Invertebrates and plants; in mammalian it may result from hypomethylation of centromere chromosome regions. The giant (endopolyploid) trophoblast cells organization includes “loose nucleosomes” accounted for by the non-canonical histone variants, i.e. H2AX, H2AZ, and H3. 3 . In the human extravillous trophoblast cells that, like murine TGC, invade endometrium, there occured significant changes of methylation as compared to non-invasive trophoblast cell populations . Meantime, some genes show hypermethylation connected with start of trophoblast lineages specification. Thus, despite the limited possibilities of chromosome visualization trophoblast cells represent an interesting model to investigate the role of modification of gene copy number and their expression that is important for the normal or abnormal cell differentiation.
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