Carty Ben L, Dunleavy Elaine M
Centre for Chromosome Biology, Biomedical Sciences, National University of Ireland Galway, Galway H91 W2TY, Ireland.
Essays Biochem. 2020 Sep 4;64(2):223-232. doi: 10.1042/EBC20190066.
Asymmetric cell division (ACD) produces daughter cells with separate distinct cell fates and is critical for the development and regulation of multicellular organisms. Epigenetic mechanisms are key players in cell fate determination. Centromeres, epigenetically specified loci defined by the presence of the histone H3-variant, centromere protein A (CENP-A), are essential for chromosome segregation at cell division. ACDs in stem cells and in oocyte meiosis have been proposed to be reliant on centromere integrity for the regulation of the non-random segregation of chromosomes. It has recently been shown that CENP-A is asymmetrically distributed between the centromeres of sister chromatids in male and female Drosophila germline stem cells (GSCs), with more CENP-A on sister chromatids to be segregated to the GSC. This imbalance in centromere strength correlates with the temporal and asymmetric assembly of the mitotic spindle and potentially orientates the cell to allow for biased sister chromatid retention in stem cells. In this essay, we discuss the recent evidence for asymmetric sister centromeres in stem cells. Thereafter, we discuss mechanistic avenues to establish this sister centromere asymmetry and how it ultimately might influence cell fate.
不对称细胞分裂（ACD）产生具有不同细胞命运的子细胞，对多细胞生物的发育和调控至关重要。表观遗传机制是细胞命运决定的关键因素。着丝粒是由组蛋白H3变体着丝粒蛋白A（CENP-A）的存在而表观遗传指定的位点，对于细胞分裂时的染色体分离至关重要。干细胞和卵母细胞减数分裂中的ACD被认为依赖着丝粒完整性来调节染色体的非随机分离。最近的研究表明，在雄性和雌性果蝇生殖系干细胞（GSC）中，CENP-A在姐妹染色单体的着丝粒之间不对称分布，更多的CENP-A位于将被分离到GSC的姐妹染色单体上。着丝粒强度的这种不平衡与有丝分裂纺锤体的时间和不对称组装相关，并可能使细胞定向，从而使干细胞中姐妹染色单体偏向保留。在本文中，我们讨论了干细胞中不对称姐妹着丝粒的最新证据。此后，我们讨论了建立这种姐妹着丝粒不对称性的机制途径，以及它最终可能如何影响细胞命运。
