Research

Project 1: Germ cell fate determination during mouse oogenesis.

A conserved phenomenon of mammalian oocyte differentiation is that only a small fraction of the fetal germ cells can become primary oocytes. The massive fetal germ cell apoptosis has been attributed to developmental defects. However, my recent work in mice suggests that fetal germ cell apoptosis is a programmed event where the dying cells sacrifice themselves by donating cytoplasmic content to the future primary oocytes. By using the single-cell lineage tracing approach in we established mice, we found that fetal germ cells derived from one progenitor (primordial germ cell) are connected via intercellular bridges, forming germline cysts. Within the cyst, organelles (Golgi complexes, mitochondria and centrosomes) are redistributed via intercellular connections, leading to two distinct germ cell fates: germ cells that donate cytoplasm undergo apoptosis; germ cells that collect cytoplasm become primary oocytes.

We are investigating: how fetal germ cells form branched cyst structure during germ cell mitosis? how fetal germ cells establish intercellular polarity that guides the cytoplasmic transport? What is the biological significance of the cytoplasmic enrichment in oocyte function? Answers to these question will provide new insights into the mechanism underling the size of ovarian reserve.

Project 2: Development-quiescence-development transitions in primary oocytes.

After oocyte differentiation completes in the fetal ovary, the majority of the primary oocytes together with the surrounding follicle cells become quiescent and serves as the only source of egg production in adulthood. In the adult ovary, a cohort of primary oocytes leaves quiescent and initiate the development into mature oocytes. We are investigating: how primary oocytes become quiescent after collecting a large amount of cytoplasmic content in the fetal ovary? What triggers quiescent primary oocytes to enter developmental phase in the adult ovary. The new mechanism underlying primary oocyte quiescence is essential for understanding pathological causes of premature ovarian failure in humans.

Project 3: Somatic cell differentiation in ovarian development and ovarian caner.

The incidence of ovarian cancer rises as women age. However, the exact cellular origins of ovarian cancer remains elusive. We are interested in characterizing the role of germ cell-somatic cell interaction in fetal ovarian somatic cell differentiation and ovarian aging. The fundamental knowledge acquired from this study will lay the foundation for identifying cellular origins of ovarian cancer.