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GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program
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GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program
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Journal Article
GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program
2021
Overview
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.
