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Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells

Shinde, Vaibhav and Brungs, Sonja and Henry, Margit and Wegener, Lucia and Nemade, Harshal and Rotshteyn, Aviseka and Baumstark-Khan, Christa and Hellweg, Christine E. and Hescheler, Jürgen and Hemmersbach, Ruth and Sachinidis, Apapios (2016) Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells. Cellular Physiology and Biochemistry, 2016 (38), pp. 1483-1499. S. Karger AG. DOI: 10.1159/000443090 ISSN 1015-8987

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Official URL: http://www.karger.com/Article/PDF/443090

Abstract

Background/Aims: Embryonic developmental studies under microgravity conditions in space are very limited. To study the effects of altered gravity on the embryonic development processes we established an in vitro methodology allowing differentiation of mouse embryonic stem cells (mESCs) under simulated microgravity within a fast-rotating clinostat (clinorotation) and capture of microarray-based gene signatures. Methods: The differentiating mESCs were cultured in a 2D pipette clinostat. The microarray and bioinformatics tools were used to capture genes that are deregulated by simulated microgravity and their impact on developmental biological processes. Results: The data analysis demonstrated that differentiation of mESCs in pipettes for 3 days resultet to early germ layer differentiation and then to the different somatic cell types after further 7 days of differentiation in the Petri dishes. Clinorotation influences differentiation as well as non-differentiation related biological processes like cytoskeleton related 19 genes were modulated. Notably, simulated microgravity deregulated genes Cyr61, Thbs1, Parva, Dhrs3, Jun, Tpm1, Fzd2 and Dll1 are involved in heart morphogenesis as an acute response on day 3. If the stem cells were further cultivated under normal gravity conditions (1 g) after clinorotation, the expression of cardiomyocytes specific genes such as Tnnt2, Rbp4, Tnni1, Csrp3, Nppb and Mybpc3 on day 10 was inhibited. This correlated well with a decreasing beating activity of the 10-days old embryoid bodies (EBs). Finally, we captured Gadd45g, Jun, Thbs1, Cyr61and Dll1 genes whose expressions were modulated by simulated microgravity and by real microgravity in various reported studies. Simulated microgravity also deregulated genes belonging to the MAP kinase and focal adhesion signal transduction pathways. Conclusion: One of the most prominent biological processes affected by simulated microgravity was the process of cardiomyogenesis. The most significant simulated microgravity-affected genes, signal transduction pathways, and biological processes which are relevant for mESCs differentiation have been identified and discussed below.

Item URL in elib:https://elib.dlr.de/105108/
Document Type:Article
Title:Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Shinde, VaibhavUniversity of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, GermanyUNSPECIFIED
Brungs, SonjaGerman Aerospace Center (DLR), Institute of Aerospace Medicine, Gravitational Biology, Cologne, GermanyUNSPECIFIED
Henry, MargitUniversity of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, GermanyUNSPECIFIED
Wegener, LuciaGerman Research Center (DLR), Institute of Aerospace Medicine, Gravitational Biology, Cologne, GermanyUNSPECIFIED
Nemade, HarshalUniversity of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, GermanyUNSPECIFIED
Rotshteyn, AvisekaUniversity of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, GermanyUNSPECIFIED
Baumstark-Khan, ChristaGerman Aerospace Center (DLR), Institute of Aerospace Medicine, Radiation Biology, Cologne, GermanyUNSPECIFIED
Hellweg, Christine E.German Aerospace Center (DLR), Institute of Aerospace Medicine, Radiation Biology, Cologne, GermanyUNSPECIFIED
Hescheler, JürgenUniversity of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, GermanyUNSPECIFIED
Hemmersbach, RuthGerman Aerospace Center (DLR), Institute of Aerospace Medicine, Gravitational Biology, Cologne, GermanyUNSPECIFIED
Sachinidis, ApapiosUniversity of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, GermanyUNSPECIFIED
Date:4 April 2016
Journal or Publication Title:Cellular Physiology and Biochemistry
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:No
Volume:2016
DOI :10.1159/000443090
Page Range:pp. 1483-1499
Publisher:S. Karger AG
ISSN:1015-8987
Status:Published
Keywords:Microgravity, Embryonic stem cells, Differentiation, Transcriptomics, Signal transduction pathways, Clinostat, Cardiomyogenesis
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Biowissenschaftliche Nutzerunterstützung, R - Vorhaben Biowissenschaftliche Exp.-vorbereitung, R - Vorhaben Strahlenbiologie
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Biomedical Research
Institute of Aerospace Medicine > Radiation Biology
Deposited By: Duwe, Helmut
Deposited On:13 Jul 2016 18:45
Last Modified:23 Jan 2019 05:02

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