A programming perspective of the germline cycle on origin of germ cell tumors and epigenetic inheritance of diseases

Germ cells provide the enduring link between generations and their development is one of the most intricate processes involving genetic and epigenetic reprogramming.

Our understanding has reached a level that it is possible to reconstitute germ cells towards the premigratory stage from stem cells.

But we still know little about the directional migration across diverse microenvironments to fully recapitulate the maturation and harness the potential to derive functional gametes in a dish.

Moreover, germline development is particularly sensitive to environmental changes partly due to its long developing period under active epigenetic remodeling.

Further investigation of molecular principles of the germline cycle will advance our knowledge in understanding of germ cell tumorigenesis and germline transmission of disease inheritance.Here, we aim to combine genetics lineage tracing with single-cell sequencing to profile germ cells along their critical developing period under physiological and pathological conditions.

By comparison, we will be able to reveal the fail-safe mechanism controlling normal development for future stem cell-based disease modeling and therapy, meanwhile identify the molecular signature of tumorigenesis.

Importantly, we will reveal epigenetic modifications through the germline that could mediate the disease inheritance across generations.

Our work is essential to synthesize the knowledge gained in germ cell biology with the implications of disease mechanisms.