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Hirota Group

Having the correct number of chromosomes (ploidy) is crucial for normal development and health. Numerical chromosome abnormalities often cause embryonic arrest and infertility, and are associated with diseases like cancer and Down syndrome. My major interest is in how ploidy is regulated in development. Using various types of mouse stem cells and germ cells as research models, we aim to reveal molecular mechanisms limiting abnormal ploidy in the body. We also investigate the role of cellular reprogramming to pluripotency in correcting the state carrying an extra chromosome. The knowledge gained will be used for establishing a novel therapy for phenotypes associated with abnormal ploidy.

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Hirota_project_1

Mechanisms limiting polyploidy in the body

This project focuses on mechanisms preventing a type of ploidy abnormality called polyploidy, the condition of carrying extra sets of complete genomes. Embryonic polyploidy strictly causes lethality before birth, accounting for about 15% of spontaneous abortions in humans. Focusing on early embryonic cells and germ cells, we analyse what happens to polyploid cells in the body, what distinct properties polyploid cells have compared to normal cells, and detailed mechanisms to prevent polyploidy in these cell lineages.

Hirota_project_2

Role of cellular reprogramming in correcting trisomy

This project focuses on the role of cellular reprogramming to pluripotency in correcting trisomy, the condition of carrying an extra chromosome. Trisomy causes a number of syndromes including Down syndrome and Klinefelter syndrome. There is no cure for trisomy and the treatments focus on managing the symptoms. We found previously that trisomy can be converted into normal chromosome number during reprogramming to induced pluripotent stem cells in mouse and human cells. This project aims to identify the molecular mechanisms of this phenomenon and exploit the knowledge gained for establishing a novel therapy for trisomic phenotypes such as male infertility.

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Takayuki was awarded a King's Prize Fellowship in 2020.

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