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Biosci Rep. 2017 Apr 20;37(2). pii: BSR20170637. doi: 10.1042/BSR20170637. Print 2017 Apr 30.

Retinoic acid combined with spermatogonial stem cell conditions facilitate the generation of mouse germ-like cells.

Dong G1, Shang Z1,2,3, Liu L1,3, Liu C1,3, Ge Y1, Wang Q1,3, Wu L1,3, Chen F1,4, Li B1, Liu X1, Xu X1, Yang H1,5, Du Y6, Jiang H6.

Author information

BGI-Shenzhen, Shenzhen, China.
Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai 200092, China.
Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, BGI-Shenzhen, Shenzhen, China.
Section of Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
James D. Watson Institute of Genome Sciences, Hangzhou, China.
BGI-Shenzhen, Shenzhen, China


Spermatogenic lineage has been directly generated in spermatogonial stem cell (SSC) conditions from human pluripotent stem cells (PSCs). However, it remains unknown whether mouse embryonic stem cells (ESCs) can directly differentiate into advanced male germ cell lineage in the same conditions. Here, we showed rather low efficiency of germ-like cell generation from mouse ESCs in SSC conditions. Interestingly, addition of retinoic acid (RA) into SSC conditions enabled efficient differentiation of mouse ESCs into germ-like cells, as shown by the activation of spermatogenesis-associated genes such as Mvh, Dazl, Prdm14, Stella, Scp1, Scp3, Stra8 and Rec8 In contrast, for cells cultured in control medium, the activation of the above genes barely occurred. In addition, RA with SSC conditions yielded colonies of Acrosin-expressing cells and the positive ratio reached a peak at day 6. Our work thus establishes a simple and cost-efficient approach for male germ like cell differentiation from mouse PSCs and may propose a useful strategy for studying spermatogenesis in vitro.


Differentiation; Germ-like cells; Retinoic acid; Spermatogonial stem cell conditions

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