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Human Primordial Germ Cells Are Specified from Lineage-Primed Progenitors

Overview
Journal Cell Rep
Publisher Cell Press
Date 2019 Dec 26
PMID 31875561
Citations 89
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Abstract

In vitro gametogenesis is the process of making germline cells from human pluripotent stem cells. The foundation of this model is the quality of the first progenitors called primordial germ cells (PGCs), which in vivo are specified during the peri-implantation window of human development. Here, we show that human PGC (hPGC) specification begins at day 12 post-fertilization. Using single-cell RNA sequencing of hPGC-like cells (hPGCLCs) differentiated from pluripotent stem cells, we discovered that hPGCLC specification involves resetting pluripotency toward a transitional state with shared characteristics between naive and primed pluripotency, followed by differentiation into lineage-primed TFAP2A progenitors. Applying the germline trajectory to TFAP2C mutants reveals that TFAP2C functions in the TFAP2A progenitors upstream of PRDM1 to regulate the expression of SOX17. This serves to protect hPGCLCs from crossing the Weismann's barrier to adopt somatic cell fates and, therefore, is an essential mechanism for successfully initiating in vitro gametogenesis.

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References
1.
Shao Y, Taniguchi K, Gurdziel K, Townshend R, Xue X, Aw Yong K . Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche. Nat Mater. 2016; 16(4):419-425. PMC: 5374007. DOI: 10.1038/nmat4829. View

2.
Magnusdottir E, Dietmann S, Murakami K, Gunesdogan U, Tang F, Bao S . A tripartite transcription factor network regulates primordial germ cell specification in mice. Nat Cell Biol. 2013; 15(8):905-15. PMC: 3796875. DOI: 10.1038/ncb2798. View

3.
Stegle O, Teichmann S, Marioni J . Computational and analytical challenges in single-cell transcriptomics. Nat Rev Genet. 2015; 16(3):133-45. DOI: 10.1038/nrg3833. View

4.
Tang W, Dietmann S, Irie N, Leitch H, Floros V, Bradshaw C . A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development. Cell. 2015; 161(6):1453-67. PMC: 4459712. DOI: 10.1016/j.cell.2015.04.053. View

5.
Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View