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Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro

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) a...

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Autores principales: Abeln, Markus, Borst, Kristina M., Cajic, Samanta, Thiesler, Hauke, Kats, Elina, Albers, Iris, Kuhn, Maike, Kaever, Volkhard, Rapp, Erdmann, Münster‐Kühnel, Anja, Weinhold, Birgit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502888/
https://www.ncbi.nlm.nih.gov/pubmed/28374933
http://dx.doi.org/10.1002/cbic.201700083
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author Abeln, Markus
Borst, Kristina M.
Cajic, Samanta
Thiesler, Hauke
Kats, Elina
Albers, Iris
Kuhn, Maike
Kaever, Volkhard
Rapp, Erdmann
Münster‐Kühnel, Anja
Weinhold, Birgit
author_facet Abeln, Markus
Borst, Kristina M.
Cajic, Samanta
Thiesler, Hauke
Kats, Elina
Albers, Iris
Kuhn, Maike
Kaever, Volkhard
Rapp, Erdmann
Münster‐Kühnel, Anja
Weinhold, Birgit
author_sort Abeln, Markus
collection PubMed
description 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.
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spelling pubmed-55028882017-07-24 Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro Abeln, Markus Borst, Kristina M. Cajic, Samanta Thiesler, Hauke Kats, Elina Albers, Iris Kuhn, Maike Kaever, Volkhard Rapp, Erdmann Münster‐Kühnel, Anja Weinhold, Birgit Chembiochem Full Papers 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. John Wiley and Sons Inc. 2017-05-11 2017-07-04 /pmc/articles/PMC5502888/ /pubmed/28374933 http://dx.doi.org/10.1002/cbic.201700083 Text en © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Full Papers
Abeln, Markus
Borst, Kristina M.
Cajic, Samanta
Thiesler, Hauke
Kats, Elina
Albers, Iris
Kuhn, Maike
Kaever, Volkhard
Rapp, Erdmann
Münster‐Kühnel, Anja
Weinhold, Birgit
Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro
title Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro
title_full Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro
title_fullStr Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro
title_full_unstemmed Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro
title_short Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro
title_sort sialylation is dispensable for early murine embryonic development in vitro
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502888/
https://www.ncbi.nlm.nih.gov/pubmed/28374933
http://dx.doi.org/10.1002/cbic.201700083
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