Modeling mammalian spermatogonial differentiation and meiotic initiation in vitro

In mammalian testes, premeiotic spermatogonia respond to retinoic
acid by completing an essential lengthy differentiation program before
initiating meiosis. The molecular and cellular changes directing these
developmental processes remain largely undefined. This wide gap in
knowledge is due to two critical unresolved technical challenges: (1)
lack of robust and reliable in vitro models to study differentiation and
meiotic initiation; and (2) lack of methods to isolate large and pure
populations of male germ cells at each stage of differentiation and at
meiotic initiation. Here, we report a facile in vitro differentiation and
meiotic initiation system that can be readily manipulated, including the
use of chemical agents that cannot be safely administered to live
animals. In addition, we present a transgenic mouse model enabling
fluorescence-activated cell sorting-based isolation of millions of
spermatogonia at specific developmental stages as well as meiotic
spermatocytes