scholarly journals SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling

Development ◽  
2018 ◽  
Vol 145 (23) ◽  
pp. dev164160 ◽  
Author(s):  
Kentaro Mochizuki ◽  
Yukiko Tando ◽  
Tamotsu Sekinaka ◽  
Kei Otsuka ◽  
Yohei Hayashi ◽  
...  
Cell Reports ◽  
2018 ◽  
Vol 24 (10) ◽  
pp. 2682-2693.e6 ◽  
Author(s):  
Kentaro Mochizuki ◽  
Yohei Hayashi ◽  
Tamotsu Sekinaka ◽  
Kei Otsuka ◽  
Yumi Ito-Matsuoka ◽  
...  

2021 ◽  
Vol 4 (5) ◽  
pp. e202000974
Author(s):  
Yoji Kojima ◽  
Chika Yamashiro ◽  
Yusuke Murase ◽  
Yukihiro Yabuta ◽  
Ikuhiro Okamoto ◽  
...  

The in vitro reconstitution of human germ-cell development provides a robust framework for clarifying key underlying mechanisms. Here, we explored transcription factors (TFs) that engender the germ-cell fate in their pluripotent precursors. Unexpectedly, SOX17, TFAP2C, and BLIMP1, which act under the BMP signaling and are indispensable for human primordial germ-cell-like cell (hPGCLC) specification, failed to induce hPGCLCs. In contrast, GATA3 or GATA2, immediate BMP effectors, combined with SOX17 and TFAP2C, generated hPGCLCs. GATA3/GATA2 knockouts dose-dependently impaired BMP-induced hPGCLC specification, whereas GATA3/GATA2 expression remained unaffected in SOX17, TFAP2C, or BLIMP1 knockouts. In cynomolgus monkeys, a key model for human development, GATA3, SOX17, and TFAP2C were co-expressed exclusively in early PGCs. Crucially, the TF-induced hPGCLCs acquired a hallmark of bona fide hPGCs to undergo epigenetic reprogramming and mature into oogonia/gonocytes in xenogeneic reconstituted ovaries. By uncovering a TF circuitry driving the germ line program, our study provides a paradigm for TF-based human gametogenesis.


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