Leukemia inhibitory factor (LIF) enhances germ cell differentiation from primate embryonic stem cells

Area of Science:

• Reproductive Biology
• Stem Cell Research
• Developmental Biology

Background:

• Embryonic stem cells (ESCs) can be differentiated into germ cells in vitro, with successful live births reported in mice.
• Deriving fully functional germ cells from primate ESCs remains a challenge, necessitating identification of key developmental factors.
• Leukemia inhibitory factor (LIF) is crucial for mouse primordial germ cell (PGC) survival but its role in primate germ cell formation is unknown.

Purpose of the Study:

• To investigate the effect of Leukemia inhibitory factor (LIF) on in vitro germ cell production from cynomolgus monkey ESCs (cyESCs).
• To determine if LIF enhances the efficiency and quality of germ cell derivation from primate ESCs.

Main Methods:

• Cynomolgus monkey ESCs (cyESCs) were cultured and differentiated for 8 days with and without LIF.
• Alkaline phosphatase activity (ALP) and expression of germ cell markers (VASA, OCT-4, BLIMP-1, SSEA-1) were analyzed.
• Meiotic gene expression was assessed to evaluate germ cell maturation stages.

Main Results:

• LIF addition resulted in dome-shaped colonies with intense alkaline phosphatase activity (ALP).
• Cells exhibited high expression of germ cell markers VASA, OCT-4, BLIMP-1, and SSEA-1, indicating early germ cell identity.
• LIF inhibited meiotic gene expression while increasing ALP-positive cells, suggesting promotion of early germ cell differentiation.

Conclusions:

• Leukemia inhibitory factor (LIF) addition significantly improves the in vitro differentiation of early germ cells from cynomolgus monkey ESCs.
• LIF appears to promote the development of early-stage germ cells rather than later meiotic stages.
• These findings are crucial for advancing primate germ cell derivation and understanding reproductive biology.