Spindle bipolarization, the process of a microtubule mass transforming into a bipolar spindle, is a prerequisite for accurate chromosome segregation. In contrast to mitotic cells, the process and mechanism of spindle bipolarization in human oocytes remains unclear. Using high-resolution imaging in more than 1800 human oocytes, we revealed a typical state of multipolar intermediates that form during spindle bipolarization and elucidated the mechanism underlying this process. We found that the minor poles formed in multiple kinetochore clusters contribute to the generation of multipolar intermediates. We further determined the essential roles of HAUS6, KIF11, and KIF18A in spindle bipolarization and identified mutations in these genes in infertile patients characterized by oocyte or embryo defects. These results provide insights into the physiological and pathological mechanisms of spindle bipolarization in human oocytes.

中文翻译：

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人卵母细胞小极介导的纺锤体双极化机制


纺锤体双极化是微管团转变为双极纺锤体的过程，是染色体精确分离的先决条件。与有丝分裂细胞相反，人类卵母细胞纺锤体双极化的过程和机制仍不清楚。通过对 1800 多个人类卵母细胞进行高分辨率成像，我们揭示了纺锤体双极化过程中形成的多极中间体的典型状态，并阐明了该过程的机制。我们发现，多个动粒簇中形成的小极有助于多极中间体的生成。我们进一步确定了 HAUS6、KIF11 和 KIF18A 在纺锤体双极化中的重要作用，并在以卵母细胞或胚胎缺陷为特征的不孕患者中鉴定了这些基因的突变。这些结果提供了对人类卵母细胞纺锤体双极化的生理和病理机制的见解。