Mouse spermatogonial stem cells (SSCs) support the life-long generation of male gamete – sperm.  Although not as well studied as the germline stem cells in lower species, mouse SSCs have been an ideal model system for the study of stem cell biology and germ cell development in mammals for decades.  However, many questions remain to be fully addressed.  Using transgenic mouse model, they purified mouse SSCs from post-natal mice and analyzed their global gene expression profiles during development.  These comparative gene expression studies suggested that changes in global gene expression occur during the establishment and differentiation of SSCs.  Numerous genes are highly enriched in SSCs, comparing to their precursor, gonocytes, and differentiated descendants, including spermatocytes and spermatids, particularly the RNA binding proteins (RBPs) that regulate messenger RNAs and protein synthesis.  Using mouse genetics, biochemical and cell biological approaches, they are continuing the analyses of their functional roles in the post-transcriptional and translational regulation and their involvement during the self-renewal and proliferation of mouse spermatogonial stem cells.

2.Post-transcriptional regulation of sperm-specific gene expression during mouse spermiogenesis.

Spermatogenesis in mouse encompassing three consecutive stages: mitosis, meiosis and cell morphogenesis.  The last stage, also called spermiogenesis, occurs when spermatocytes complete meiosis and enter the post-meiotic development during which round, haploid spermatids are transformed into mature, whip-like spermatozoa with biological functions.  The morphogenesis of spermatids has fascinated biologists for decades, however, the underlying molecular mechanisms remain poorly defined.  Through the analyses of sperm-specific protein AKAP3 (Protein kinase A anchoring protein 3), they found that multiple RNA binding proteins and PKA signaling pathway play important roles in regulating gene expression during spermiogenesis.  RNA binding protein complex and PKA signaling may participate in the regulation of messenger RNAs and influence their translational activities in response to environmental stimuli during the elongating stage of spermiogenesis.  Combining biochemical, cellular and molecular approaches, they are dissecting the relationships among the RNA binding proteins and mechanisms by which signaling pathways participate in the cellular morphogenesis of sperm.

3. Cell fate determination during mouse early embryogenesis.

One of the highly debated questions in stem cell and developmental biology is that how the cell fate of a particular cell type (like germ cells) is determined at the earliest time of embryonic development in mammals.  Germ cells are among the first cell lineages that are specialized during early development.  In lower species, including Drosophila and C. elegans, they are determined during as early as the first cell division by maternal factors inherited from female germ cells – the eggs.  However, it is not clear how cell fate determination is regulated during mammalian early embryogenesis. Their work suggested that mitochondrial ribosomal RNAs (16S mtrRNA) participate in the cell lineage formation at the early hours of mouse embryogenesis. They are conducting experiments to further characterize the potential roles of mtrRNAs during mouse pre-implantation embryogenesis.