title: Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro.
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.
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Abeln
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Borst
authors.affiliation: Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106, Magdeburg, Germany.
authors.forename: Samanta
authors.identifier: 0000-0001-5820-0732
authors.initials: S
authors.lastname: Cajic
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Thiesler
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Elina
authors.initials: E
authors.lastname: Kats
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Albers
authors.affiliation: TWINCORE Centre for Experimental and Clinical Infection Research GmbH, A joint venture between Hannover Medical School, Feodor-Lynen-Strasse 7, 30625, Hannover, Germany.|Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Braunschweig, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Kuhn
authors.affiliation: Research Core Unit Metabolomics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.affiliation: Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106, Magdeburg, Germany.|glyXera GmbH, Leipziger Strasse 44, 39120, Magdeburg, Germany.
authors.forename: Erdmann
authors.initials: E
authors.lastname: Rapp
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Münster-Kühnel
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Weinhold
mesh_terms: D000606:Amino Sugars / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004622:Embryo, Mammalian; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D018703:Founder Effect; D005690:Galactose / Q000378:metabolism; D015870:Gene Expression; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism*; D006001:Glycoconjugates / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D000216:N-Acylneuraminate Cytidylyltransferase / Q000172:deficiency* / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D000606:Amino Sugars; D006001:Glycoconjugates; D012794:Sialic Acids; C000458:N-acetyllactosamine; D000216:N-Acylneuraminate Cytidylyltransferase; D005690:Galactose
keywords: CMP-sialic acid synthase; differentiation; glycosylation; metabolism; sialic acids