Chromosomal errors in human eggs are a leading cause of miscarriages and infertility. These errors result from chromosome missegregations during the maturation of oocytes into eggs. Chromosome segregation is driven by the spindle, a macromolecular machinery that pulls chromosomes apart. However, human oocytes often assemble unstable spindles, favoring chromosome missegregations. So. discovered that human oocyte spindles are unstable because they are deficient in the molecular motor KIFC1.
NUMA was similarly enriched at the spindle poles in bovine and porcine oocytes, which naturally lack centrosomes, as well as in mouse oocytes that we artificially depleted of acentriolar microtubule organizing centers . We thus asked whether spindle instability is a general feature of mammalian oocytes that use NUMA for spindle pole organization.
Using an RNA interference screen of proteins with diverse functions in spindle organization, we identified the molecular motor KIFC1 as a spindle-stabilizing factor that is present in other mammalian oocytes but deficient in human oocytes. Depletion of KIFC1 in other mammalian oocytes recapitulated the spindle instability of human oocytes, resulting in spindles with unstable poles and an increase in aneuploidy.
Our data also elucidate a cause of spindle instability in human oocytes: Human oocytes are deficient in KIFC1, a key spindle-stabilizing protein in other mammalian oocytes and in cancer cells. KIFC1 stabilizes the spindle poles and prevents their fragmentation. This is likely achieved through the formation of static cross-links along parallel microtubules at the poles and the alignment of antiparallel microtubules in the central region of the spindle.
By delivering a defined amount of KIFC1 protein into human oocytes, we were able to reduce spindle instability and the risk of aneuploidy in human oocytes. Thus, our data also reveal a potential method for increasing the fidelity of spindle assembly and chromosome segregation in human oocytes.
The photo doesn't upload to my phone. I see that it's the UK so it must mean New York (my IP address) wants me to insult them. Are they a pdophile news magazine? It is England.
Great to have my work on again after the 2019 paper on the liquid-like meiotic spindle domain (LISD) in mammalian oocytes (