Focusing on female reproductive health is a keyway of dealing with population aging. Around 20 – 50% of human eggs are aneuploid, carrying too many or too few chromosomes. Aneuploidy in eggs results in abnormally developed embryos, leading to infertility, miscarriages, and genetic disorders such as Down Syndrome. The leading cause of aneuploidy in eggs is chromosome segregation errors during meiotic maturation of oocytes. Thus, elucidating the origin of chromosome segregation errors during female meiosis is of great importance for female reproduction and assisted human reproduction.
During his Ph.D., Chun So first optimized the revolutionary acute protein degradation technique Trim-Away, which was pivotal for his subsequent groundbreaking work on the chromosome segregation machineries (spindles) in eggs. By performing a systematic protein localization screen of 70 different proteins, he discovered the previously undescribed liquid-like meiotic spindle domain (LISD) around the spindles in different mammalian eggs. By combining Trim-Away, biochemical and biophysical techniques, he demonstrated that the LISD is formed by liquid-liquid phase separation and acts as a dynamic reservoir to sequester and mobilize centrosomal proteins with microtubule regulatory functions to promote acentrosomal spindle assembly.
Using different mammalian models and a genetic screen, So further identified the minus-end-directed kinesin KIFC1 as a key determinant of spindle stability in oocytes. He discovered that KIFC1 is highly expressed in most mammalian oocytes but deficient in human oocytes. By introducing exogenous KIFC1 protein, he successfully improved the fidelity of spindle assembly and chromosome segregation in human oocytes. Thus, for the first time, he proposed a therapeutic strategy to reduce aneuploidy in human eggs.
So’s findings have great potentials to be translated to fertility clinics to improve the efficiency and outcome of assisted human reproduction, boosting female fertility.
