RT Journal Article
SR Electronic
T1 GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000974
DO 10.26508/lsa.202000974
VO 4
IS 5
A1 Yoji Kojima
A1 Chika Yamashiro
A1 Yusuke Murase
A1 Yukihiro Yabuta
A1 Ikuhiro Okamoto
A1 Chizuru Iwatani
A1 Hideaki Tsuchiya
A1 Masataka Nakaya
A1 Tomoyuki Tsukiyama
A1 Tomonori Nakamura
A1 Takuya Yamamoto
A1 Mitinori Saitou
YR 2021
UL https://www.life-science-alliance.org/content/4/5/e202000974.abstract
AB 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.