Universität zu Köln

Shinde, Vaibhav, Brungs, Sonja, Henry, Margit, Wegener, Lucia, Nemade, Harshal, Rotshteyn, Tamara, Acharya, Aviseka, Baumstark-Khan, Christa, Hellweg, Christine E., Hescheler, Juergen, Hemmersbach, Ruth and Sachinidis, Agapios (2016). Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells. Cell. Physiol. Biochem., 38 (4). S. 1483 - 1500. BASEL: KARGER. ISSN 1421-9778

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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, Thbsl, Parva, Dhrs3, Jun, Tpml, Fzd2 and Dill 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, Tnnil, 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, Thbsl, Cyr6land Dill 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. (C) 2016 The Author(s) Published by S. Karger AG, Basel

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Shinde, Vaibhav UNSPECIFIED UNSPECIFIED UNSPECIFIED Brungs, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Henry, Margit UNSPECIFIED UNSPECIFIED UNSPECIFIED Wegener, Lucia UNSPECIFIED UNSPECIFIED UNSPECIFIED Nemade, Harshal UNSPECIFIED UNSPECIFIED UNSPECIFIED Rotshteyn, Tamara UNSPECIFIED UNSPECIFIED UNSPECIFIED Acharya, Aviseka UNSPECIFIED UNSPECIFIED UNSPECIFIED Baumstark-Khan, Christa UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellweg, Christine E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Hemmersbach, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-292495
DOI:	10.1159/000443090
Journal or Publication Title:	Cell. Physiol. Biochem.
Volume:	38
Number:	4
Page Range:	S. 1483 - 1500
Date:	2016
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1421-9778
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PREIMPLANTATION DEVELOPMENT; IMPACT; FERTILIZATION; CYTOSKELETON; SPACEFLIGHT; PREGNANCY Multiple languages Cell Biology; Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29249