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Radiation Response of Murine Embryonic Stem Cells

Hellweg, Christine E. and Shinde, Vaibhav and Srinivasan, Sureshkumar Perumal and Henry, Margit and Rotshteyn, Tamara and Baumstark-Khan, Christa and Schmitz, Claudia and Feles, Sebastian and Spitta, Luis F. and Hemmersbach, Ruth and Hescheler, Jürgen and Sachinidis, Agapios (2020) Radiation Response of Murine Embryonic Stem Cells. Cells, 9 (7), p. 1650. Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/cells9071650. ISSN 2073-4409.

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Official URL: http://dx.doi.org/10.3390/cells9071650

Abstract

To understand the mechanisms of disturbed differentiation and development by radiation, murine CGR8 embryonic stem cells (mESCs) were exposed to ionizing radiation and differentiated by forming embryoid bodies (EBs). The colony forming ability test was applied for survival and the MTT test for viability determination after X-irradiation. Cell cycle progression was determined by flow cytometry of propidium iodide-stained cells, and DNA double strand break (DSB) induction and repair by γH2AX immunofluorescence. The radiosensitivity of mESCs was slightly higher compared to the murine osteoblast cell line OCT-1. The viability 72 h after X-irradiation decreased dose-dependently and was higher in the presence of leukemia inhibitory factor (LIF). Cells exposed to 2 or 7 Gy underwent a transient G2 arrest. X-irradiation induced γH2AX foci and they disappeared within 72 h. After 72 h of X-ray exposure, RNA was isolated and analyzed using genome-wide microarrays. The gene expression analysis revealed amongst others a regulation of developmental genes (Ada, Baz1a, Calcoco2, Htra1, Nefh, S100a6 and Rassf6), downregulation of genes involved in glycolysis and pyruvate metabolism whereas upregulation of genes related to the p53 signaling pathway. X-irradiated mESCs formed EBs and differentiated toward cardiomyocytes but their beating frequencies were lower compared to EBs from unirradiated cells. These results suggest that X-irradiation of mESCs deregulate genes related to the developmental process. The most significant biological processes found to be altered by X-irradiation in mESCs were the development of cardiovascular, nervous, circulatory and renal system. These results may explain the X-irradiation induced-embryonic lethality and malformations observed in animal studies.

Item URL in elib:https://elib.dlr.de/135670/
Document Type:Article
Title:Radiation Response of Murine Embryonic Stem Cells
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iDORCID Put Code
Hellweg, Christine E.UNSPECIFIEDhttps://orcid.org/0000-0002-2223-3580UNSPECIFIED
Shinde, VaibhavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Srinivasan, Sureshkumar PerumalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henry, MargitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rotshteyn, TamaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumstark-Khan, ChristaUNSPECIFIEDhttps://orcid.org/0000-0002-9329-0128UNSPECIFIED
Schmitz, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feles, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spitta, Luis F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hemmersbach, RuthUNSPECIFIEDhttps://orcid.org/0000-0001-5308-6715UNSPECIFIED
Hescheler, JürgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sachinidis, AgapiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date:9 July 2020
Journal or Publication Title:Cells
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:9
DOI:10.3390/cells9071650
Page Range:p. 1650
Publisher:Multidisciplinary Digital Publishing Institute (MDPI)
ISSN:2073-4409
Status:Published
Keywords:embryonic stem cells; radiation; cell viability; cell cycle; gene expression; cell death; Kyoto Encyclopedia of genes and genomes; gene ontology
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 - Research under Space Conditions
DLR - Research theme (Project):R - Vorhaben Strahlenbiologie (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Radiation Biology
Institute of Aerospace Medicine > Gravitational Biology
Deposited By: Kopp, Kerstin
Deposited On:31 Jul 2020 09:48
Last Modified:24 Oct 2023 15:17

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