1. Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro.
- Author
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Abeln M, Borst KM, Cajic S, Thiesler H, Kats E, Albers I, Kuhn M, Kaever V, Rapp E, Münster-Kühnel A, and Weinhold B
- Subjects
- Amino Sugars metabolism, Animals, Cell Differentiation, Cell Line, Embryo, Mammalian, Embryoid Bodies cytology, Embryoid Bodies metabolism, Founder Effect, Galactose metabolism, Gene Expression, Germ Layers cytology, Glycoconjugates metabolism, HEK293 Cells, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mouse Embryonic Stem Cells cytology, Myocytes, Cardiac cytology, N-Acylneuraminate Cytidylyltransferase genetics, Pluripotent Stem Cells cytology, Transcriptome, Germ Layers metabolism, Mouse Embryonic Stem Cells metabolism, Myocytes, Cardiac metabolism, N-Acylneuraminate Cytidylyltransferase deficiency, Pluripotent Stem Cells metabolism, Sialic Acids metabolism
- Abstract
The negatively charged nonulose sialic acid (Sia) is essential for murine development in vivo. In order to elucidate the impact of sialylation on differentiation processes in the absence of maternal influences, we generated mouse embryonic stem cell (mESC) lines that lack CMP-Sia synthetase (CMAS) and thereby the ability to activate Sia to CMP-Sia. Loss of CMAS activity resulted in an asialo cell surface accompanied by an increase in glycoconjugates with terminal galactosyl and oligo-LacNAc residues, as well as intracellular accumulation of free Sia. Remarkably, these changes did not impact intracellular metabolites or the morphology and transcriptome of pluripotent mESC lines. Moreover, the capacity of Cmas
-/- mESCs for undirected differentiation into embryoid bodies, germ layer formation and even the generation of beating cardiomyocytes provides first and conclusive evidence that pluripotency and differentiation of mESC in vitro can proceed in the absence of (poly)sialoglycans., (© 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)- Published
- 2017
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