The chromatin accessibility landscape reveals distinct transcriptional regulation in the induction of human primordial germ cell-like cells from pluripotent stem cells

Summary In vitro induction of human primordial germ cell-like cells (hPGCLCs) provides an ideal platform to recapitulate hPGC development. However, the detailed molecular mechanisms regulating the induction of hPGCLCs remain largely uncharacterized. Here, we profiled the chromatin accessibility and transcriptome dynamics throughout the process of hPGCLC induction. Genetic ablation of SOX15 indicated the crucial roles of SOX15 in the maintenance of hPGCLCs. Mechanistically, SOX15 exerted its roles via suppressing somatic gene expression and sustaining latent pluripotency. Notably, ETV5, a downstream regulator of SOX15, was also uncovered to be essential for hPGCLC maintenance. Finally, a stepwise switch of OCT4/SOX2, OCT4/SOX17, and OCT4/SOX15 binding motifs were found to be enriched in closed-to-open regions of human embryonic stem cells, and early- and late-stage hPGCLCs, respectively. Collectively, our data characterized the chromatin accessibility and transcriptome landscapes throughout hPGCLC induction and defined the SOX15-mediated regulatory networks underlying this process.
Graphical abstract
Highlights • Chromatin accessibility landscape is revealed throughout hPGCLC induction • SOX15 is involved in hPGCLC maintenance via dual effects • ETV5, a downstream regulator of SOX15, is essential for hPGCLC maintenance • A stepwise OCT4:SOX motifs switch is uncovered throughout hPGCLC induction
Zhao and colleagues reveals the chromatin accessibility and transcriptome dynamics throughout hPGCLC induction. They show the essential roles of SOX15-mediated regulatory network in maintaining the hPGCLC identity by suppressing somatic gene expression and sustaining latent pluripotency. Moreover, they uncover a stepwise OCT4:SOX motifs switch throughout hPGCLC induction.