《科学进展》论文：胚胎靠平衡纺锤体拉力护住脆弱的Y染色体，轻微压力下Y纠错成功率比其它染色体低2.5倍
英国弗朗西斯·克里克研究所的一项研究，揭示了胚胎在发育最初几天如何保护容易丢失的 Y 染色体。论文发表于《科学进展》期刊，Phys.org 于11月9日作了报道。研究由该所性别染色体生物学实验室负责人 James Turner 与其实验室前博士后研究员 Agata Zielinska 完成。
Y 染色体决定雄性发育，体量虽小却作用重大；细胞衰老过程中常丢失 Y 染色体，这与癌症、阿尔茨海默病与心脏病等状况相关。Turner 表示，Y 染色体在细胞分裂时很脆弱，但若它在发育最初几天—即胚胎需要靠它开启雄性发育之时—丢失，会发生什么此前并不清楚。胚胎早期若丢失一条染色体通常无法存活，但有一类人多数或部分细胞只有一条 X 染色体，即特纳综合征（Turner syndrome），影响生长与生育并可能带来心血管、肾脏与自身免疫并发症；该综合征常被认为与第二条 X 的丢失有关，也可由 Y 的丢失造成，Turner 认为后者可能比此前所想更常见。
机制上，细胞分裂前各染色体成对排到细胞中央，纺锤体微管牵引着丝粒把它们拉入两个新细胞；而 Y 染色体的着丝粒处，一种构成牵引「着陆台」基础的蛋白水平异常低，天生处于劣势。Zielinska 用荧光标记小鼠受精卵第一次分裂中的染色体并在显微镜下记录：正常条件下，多数 Y 染色体对在第一次分裂中成功分离，保障机制包括精细平衡的纺锤体拉力—Y 所受张力小于其它染色体。但当细胞受到轻微压力（以弱化纺锤体模拟）时，Y 染色体对常无法排齐、在纺锤体周围漂浮，且胚胎在分裂前纠正这一错误的可能性比对其它染色体低2.5倍。团队进一步把一个 XY 细胞与一个 XO 细胞组合成「嵌合」胚胎模型：这类胚胎小于完整的 XY 胚胎，但随时间推移 XY 细胞逐渐胜出、占比上升，显示胚胎会以偏向 XY 细胞的方式部分弥补 Y 的丢失。Turner 表示，胚胎显然有显著能力缓冲性染色体丢失；该实验室下一步希望找出体内哪些压力会让 Y 更难完成关键的第一次分裂。
Science Advances Study: Embryos Protect the Vulnerable Y Chromosome With Finely Balanced Spindle Forces; Under Mild Stress, Y Errors Are 2.5 Times Less Likely t
A study from the Francis Crick Institute in the United Kingdom has shown how embryos protect the easily lost Y chromosome in the earliest days of development. The paper, by James Turner, who runs the Crick's Sex Chromosome Biology Laboratory, and Agata Zielinska, a former postdoctoral researcher in the lab, was published in Science Advances and reported by Phys.org on November 9.
The Y chromosome confers male sex and plays a big role in development and health despite its small size; as cells age they frequently lose their Y chromosomes, which is associated with conditions like cancer, Alzheimer's disease and heart disease. Turner said the Y chromosome is vulnerable as cells divide, with consequences for health, but what happens if it is lost in the earliest days of development, when it needs to switch on male sex in the embryo, was unclear. Embryos do not usually survive if a chromosome is lost early in development, but individuals can have Turner syndrome, in which most or some cells have only one X chromosome, affecting growth and fertility and causing potential cardiovascular, renal and autoimmune complications. Turner syndrome is often thought to be linked to loss of the second X, but it can also result from loss of a Y, which Turner believes may happen more often than previously thought.
Mechanistically, before cell division, two copies of each chromosome line up in the middle of the cell and spindles pull them apart via the centromere landing pad; the Y chromosome has unusually low levels of a protein that forms the foundations of that landing pad, starting at a disadvantage. Zielinska fluorescently labelled chromosomes in mouse zygotes during their first division and recorded them duplicating, lining up and splitting under a microscope. In normal conditions, most Y chromosome pairs separated in the first division, helped by safeguards including finely balanced spindle forces that put the Y under less tension than other chromosomes. But if cells were even mildly stressed, simulated by weakening the spindles, the Y pairs often failed to line up and floated around the spindle, and embryos were 2.5 times less likely to correct this error before dividing than they were for other chromosomes, Zielinska said. She then combined an XY and an XO cell into a mosaic embryo model: those embryos were smaller than fully XY embryos, but over time the XY cells started to outcompete the XO cells, gradually shifting the balance toward cells with both sex chromosomes. Turner concluded that the embryo has a remarkable ability to buffer against sex chromosome loss despite the Y's vulnerability. The lab now aims to identify stresses in the body that make it harder for the Y chromosome to complete its crucial first division.
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来源：《科学进展》期刊论文（经 Phys.org 报道
发布：GSM·美国（发布链接）
图片来源：细胞核显微图像（资料图）。（Wikimedia Commons／CC BY-SA 3.0）|A cell nucleus under the microscope (file photo). (Wikimedia Commons / CC BY-SA 3.0)
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