Peroxisomes in maintenance and neural differentiation of mESCs

Peroxisomes are single-membrane bound organelles playing important roles in cellular lipid and reactive oxygen species (ROS) metabolism. Defective peroxisome biosynthesis, assembly or biochemical functions leads to a group of autosomal recessive disorders called peroxisome biogenesis disorders (PBDs). PBDs can affect most organs of the body, with common findings of visual, auditory and neurological deterioration. In this study, we disrupted peroxisome assembly by deleting PEX5 or PEX19, two essential peroxisome biogenesis factors, in mouse embryonic stem cells (mESCs), and analyzed the impacts of peroxisome deficiency on mESC maintenance and neural differentiation in vitro. Our results reveal that peroxisome deficiency impaired mouse stem cell self-renewal for enhanced cell death and loss of pluripotency. Increased ROS and defective synthesis of plasmalogens at least partially account for the phenotypes. Finally, the peroxisome deficient cells fail to differentiate to neuron stem cells, confirming that peroxisomes are important for ES cell maintenance and neural differentiation.