DNA methyltransferase-3-dependent nonrandom template segregation in differentiating embryonic stem cells
DNA methyltransferase-3-dependent nonrandom template segregation in differentiating embryonic stem cells
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DOI：
10.1083/jcb.201307110
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发表时间：
2013-10-14
影响因子：
7.8
通讯作者：
Conboy, Michael J.
中科院分区：
文献类型：
--
作者：
Elabd, Christian;Cousin, Wendy;Conboy, Michael J.
细胞命运的对称性是干细胞的一个基本特性，其中一个子细胞自我更新，而另一个子细胞分化。在系统发育不同的生物，如植物、真菌和哺乳动物，在不对称细胞分裂过程中染色体的非随机模板分离（NRTS）的证据已经被证明。然而，在此之前，染色单体的不对称遗传从未在胚胎干细胞（ESCs）分化中得到证实，其分子机制仍然未知。我们的结果明确地证明了NRTS在不对称分裂、分化人和小鼠内皮细胞中的作用。此外，我们发现NRTS依赖于DNA甲基化和Dnmt3 (DNA甲基转移酶-3)，表明调控这一现象的分子机制。此外，我们的数据支持这样的假设，即染色单体与“旧”模板DNA的保留保留了细胞命运的表观遗传记忆，而“新”DNA链和DNA甲基转移酶定位到谱系注定的子细胞有助于表观遗传适应新的细胞命运。
A symmetry of cell fate is one fundamental property of stem cells, in which one daughter cell self-renews, whereas the other differentiates. Evidence of nonrandom template segregation (NRTS) of chromosomes during asymmetric cell divisions in phylogenetically divergent organisms, such as plants, fungi, and mammals, has already been shown. However, before this current work, asymmetric inheritance of chromatids has never been demonstrated in differentiating embryonic stem cells (ESCs), and its molecular mechanism has remained unknown. Our results unambiguously demonstrate NRTS in asymmetrically dividing, differentiating human and mouse ESCs. Moreover, we show that NRTS is dependent on DNA methylation and on Dnmt3 (DNA methyltransferase-3), indicating a molecular mechanism that regulates this phenomenon. Furthermore, our data support the hypothesis that retention of chromatids with the "old" template DNA preserves the epigenetic memory of cell fate, whereas localization of "new" DNA strands and de novo DNA methyltransferase to the lineage-destined daughter cell facilitates epigenetic adaptation to a new cell fate.