Uncovering the Molecular Program for Human Germ Cell Fate
2020年9月29日 15:30 - 16:30
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge
How can germ cells, egg and sperm, maintain immortality over the generations by resetting totipotency? The early germ cell development demonstrates particularly unique events such as global epigenetic programming. However, to date, human germline research has been hampered by the lack of amenable experimental models due to the inaccessibility to human early embryos. To achieve a breakthrough, we established a robust cell culture model to recapitulate early germline development using human ES cells and iPS cells (Irie et al., Cell 2015). By combining an extensive characterization of in vivo human fetal germ cells, we identified SOX17 and BLIMP1 as essential transcription factors driving primordial germ cell specification. The cell fate decision was firmly regulated by the balance and the timing of the expression of SOX17 and BLIMP1. Notably, the involvement of SOX17 in early germline was observed in human, monkey and pig but not in mouse and rat, which might be due to the differences in early embryogenesis. These findings are now providing unprecedented opportunities to further explore human germ cell biology for elucidating human reproduction, germ cell disorders, as well as the transmission of genetic and epigenetic information that impacts on human health and evolution.