The key enzyme of the sialic acid metabolism is involved in embryoid body formation and expression of marker genes of germ layer formation

• Published in: International journal of molecular sciences Vol. 14; no. 10; pp. 20555 - 20563
• Main Authors: Weidemann, Wenke, Hering, Jessica, Bennmann, Dorit, Thate, Annett, Horstkorte, Rüdiger
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.10.2013; Molecular Diversity Preservation International (MDPI)
• Subjects: Acids; Animals; Biomarkers - metabolism; Biosynthesis; Cell Differentiation - physiology; Cell Proliferation; Cells, Cultured; embryoid bodies; Embryoid Bodies - metabolism; embryonic stem cells; Embryonic Stem Cells - metabolism; Enzymes; Gene expression; Germ Layers - metabolism; Glycoproteins; Kinases; Metabolism; Mice; Multienzyme Complexes - deficiency; Multienzyme Complexes - metabolism; N-Acetylneuraminic Acid - metabolism; sialic acid biosynthesis; Stem cells; UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms141020555

The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are negatively charged nine carbon amino sugars and are found on most glycoproteins and many glycolipids in terminal positions, where they are involved in a variety of biological important molecular interactions. Inactivation of the GNE by homologous recombination results in early embryonic lethality in mice. Here, we report that GNE-deficient embryonic stem cells express less differentiation markers compared to wild-type embryonic stem cells. As a result, GNE-deficient embryonic stem cells fail to form proper embryoid bodies (EB) within the first day of culture. However, when culturing these cells in the presence of sialic acids for three days, also GNE-deficient embryonic stem cells form normal EBs. In contrast, when culturing these cells in sialic acid reduced medium, GNE-deficient embryonic stem cells proliferate faster and form larger EBs without any change in the expression of markers of the germ layers.