Details

Autor(en) / Beteiligte

• Sugawa, Fumihiro
• Araúzo-Bravo, Marcos J
• Yoon, Juyong
• Kim, Kee-Pyo
• Aramaki, Shinya
• Wu, Guangming
• Stehling, Martin
• Psathaki, Olympia E
• Hübner, Karin
• Schöler, Hans R

Titel

Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile

Ist Teil von

• The EMBO journal, 2015-04, Vol.34 (8), p.1009-1024

Ort / Verlag

London: Blackwell Publishing Ltd

Erscheinungsjahr

2015

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo . The molecular mechanisms underlying human PGC specification are poorly understood due to inaccessibility of cell materials and lack of in vitro models for tracking the earliest stages of germ cell development. Here, we describe a defined and stepwise differentiation system for inducing pre‐migratory PGC‐like cells (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans is similar to the murine process, with the sequential activation of mesodermal and PGC genes, and the suppression of neural induction and of de novo DNA methylation, suggesting that human PGC formation is induced via epigenesis, the process of germ cell specification via inductive signals from surrounding somatic cells. This study demonstrates that PGC commitment in humans shares key features with that of the mouse, but also highlights key differences, including transcriptional regulation during the early stage of human PGC development (3–6 weeks). A more comprehensive understanding of human germ cell development may lead to methodology for successfully generating PSC‐derived gametes for reproductive medicine. Synopsis Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) in vitro from pluripotent stem cells (PSCs). This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine. PSCs differentiate first into a heterogeneous mesoderm‐like cell population and then into PGCLCs. PGCLCs exhibit minimal expression of the PGC gene PRDM14 . PGC specification in humans is similar to the murine process in that mesodermal and PGC genes are sequentially activated and neural induction and de novo DNA methylation are suppressed. Differences to the murine process include transcriptional regulation during the early stages of human PGC development (3–6 weeks). Graphical Abstract Primordial germ cells (PGCs) generate sperm and oocytes. A defined differentiation system induces human pre‐migratory PGC‐like cells (PGCLCs) from pluripotent stem cells (PSCs) in vitro . This protocol allows disease modeling and may lead to the generation of gametes for reproductive medicine.