Stem Cell Pathology
- Conserved mechanisms during sexual reproduction and germ cell development
- Protection of the genome by small RNAs
- Function and regulation of parentally inherited genes
- Genome reprogramming during germ cell development
Conserved mechanisms during sexual reproduction and germ cell development
Non-coding small RNA known as piRNAs (PIWI interacting RNA) bind with mouse PIWI family proteins and play an important role in spermatogenesis. The lab has revealed that piRNA regulates the expression of mobile genetic elements, called retrotransposons, by DNA methylation [1-3]. Based on these results, the lab is trying to elucidate how small RNA facilitates epigenetic regulation. DNA methylation is analyzed using next generation sequencing and epigenetic editing technology to determine how small RNA play a role in the process of spermatogenesis.
While most human genes are expressed from both chromosomes, some are only expressed from one parentally inherited chromosome in a process called genomic imprinting. The imprinted genes play important roles in various developmental processes such as placenta formation, fetal growth, higher brain function, and the maintenance of bone marrow stem cells. The expression of the imprinted gene is controlled by epigenetic modifications that fluctuate dynamically during fertilization and subsequent development. How the allelic expression of imprinted genes is maintained is unknown, however. Many of the functions and regulatory mechanisms of imprinting genes are also unknown. The lab seeks to resolve these questions using knockout mice, early embryos, cultured stem cells and additional systems.
1. Miyagawa et al. Genes Dev, 22:918-30 (2008)
2. Miyagawa et al. Genes Dev, 24:887-892 (2010)
3. Kojima et al. Cell Rep, 16(11):2819-28 (2016)