Program Leaders
The Program in Human Development and Reproduction focuses on the establishment of innovative approaches to study the key processes needed for the production of healthy offspring. The Program nucleates a multidisciplinary group of scientists uniquely poised to impact basic and translational research. Program members have made significant advances in understanding the differentiation of germ cells and early gonadal somatic cells, fertilization, embryo development, and endometrial biology. We stimulate the application of state-of-the-art approaches to brake technical barriers and address large unsolved questions or clinical problems.
Recent breakthroughs by our scientists:
In vitro derivation of human spermatogonia and spermatozoa is of paramount importance to recover male fertility, which can be lost by developmental errors that occur during spermatogenesis or by gonadotoxic insults. To this end, Sasaki lab has developed the robust culture method to reconstitute male germ cells using pluripotent stem cells in humans and non-human primates. Recently, Sasaki lab successfully established an in vitro induction method for human prospermatogonia-like cells from hPGCLCs using xenogeneic reconstituted testes (xrTestes). In this system, hPGCLCs mature into prospermatogonia-like cells that exhibit features of epigenetic reprogramming, including genome-wide DNA demethylation, and bear a close resemblance to prospermatogonia in 2nd trimester human testes as assessed by single cell RNA-sequencing (scRNA-seq) (Nature Communs 2020, 11:5656). As hiPSCs-derived gamete generation is limited by ethical and safety concerns, we are developing preclinical model systems using rhesus monkeys and common marmosets. To date, we have characterized pre-migratory marmoset PGCs at E50 embryos by scRNA-seq and successfully established robust methods to induce marmoset iPSCs into PGCLCs that bear a remarkable immunophenotypic and transcriptomic similarity to pre-migratory PGCs in vivo (eLife 2023).
