Mehrotra Sonam, Deshpande Girish
Department of Biology, Indian Institute of Science Education and Research Pune.
Department of Molecular Biology, Princeton University.
Genes Genet Syst. 2018 Feb 10;92(4):163-172. doi: 10.1266/ggs.16-00057. Epub 2017 Jun 30.
Adult stem cells are capable of both symmetric and asymmetric cell divisions. Asymmetric cell division allows self-renewal and gives rise to intermediate cells that ultimately differentiate into specific cell types. Consequently, adult stem cells play a key role in development and tissue homeostasis during the life span of an organism. Typically, adult stem cell divisions are regulated through coordination between non-autonomous signaling from the niche and cell-autonomous influences from stem cell-intrinsic factors. Although localized distribution of proteins, RNA and organelles during cell division contributes significantly to the differences between fates of daughter cells, recent studies have also implicated epigenetic factors in this process. A number of epigenetic modifications remain associated with the chromosomes during mitosis and serve as a template to reestablish fates after mitosis. Whether the distribution of epigenetic modifications is random on each chromatid or there is a bias in their distribution is therefore under extensive investigation. The nonrandom distribution of epigenetic modifications on mitotic chromosomes provides an attractive possible explanation of how bias is generated during chromatid segregation. In Drosophila male germline stem cells, the histone modifications present in the stem cells are distinct from those in the differentiating daughter cells. These modifications help to retain pre-existing histones in the mother cell while imparting newly synthesized histones to the daughter cell. Importantly, the retention of pre-existing histones in the stem cells is a prerequisite to maintain their ability to self-renew. Here we summarize recent studies that focus on the role of different epigenetic modifications in the regulation of asymmetric adult germline stem cell divisions in Drosophila. We further describe how epigenetic modifications potentially lead to variations in the otherwise equivalent chromatids, and discuss the role of biased chromatid segregation in asymmetric cell divisions.
成体干细胞能够进行对称和不对称细胞分裂。不对称细胞分裂允许自我更新，并产生最终分化为特定细胞类型的中间细胞。因此，成体干细胞在生物体的生命周期中对发育和组织稳态起着关键作用。通常，成体干细胞的分裂是通过来自微环境的非自主信号与干细胞内在因子的细胞自主影响之间的协调来调节的。尽管细胞分裂过程中蛋白质、RNA和细胞器的局部分布对 daughter 细胞命运的差异有显著贡献，但最近的研究也表明表观遗传因素参与了这一过程。许多表观遗传修饰在有丝分裂期间仍与染色体相关联，并作为有丝分裂后重新建立细胞命运的模板。因此，表观遗传修饰在每个染色单体上的分布是随机的还是存在分布偏差，正在受到广泛研究。有丝分裂染色体上表观遗传修饰的非随机分布为染色单体分离过程中如何产生偏差提供了一个有吸引力的可能解释。在果蝇雄性生殖系干细胞中，干细胞中存在的组蛋白修饰与分化的 daughter 细胞中的不同。这些修饰有助于在母细胞中保留预先存在的组蛋白，同时将新合成的组蛋白赋予 daughter 细胞。重要的是，在干细胞中保留预先存在的组蛋白是维持其自我更新能力的先决条件。在这里，我们总结了最近的研究，这些研究聚焦于不同表观遗传修饰在果蝇不对称成体生殖系干细胞分裂调控中的作用。我们进一步描述了表观遗传修饰如何潜在地导致原本等同的染色单体出现差异，并讨论了有偏差的染色单体分离在不对称细胞分裂中的作用。
