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Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure

The biological effects of low-dose ionizing radiation (LDIR) exposure in humans are not comprehensively understood, generating a high degree of controversy in published literature. The earliest stages of human development are known to be among the most sensitive to stress exposures, especially genot...

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Autores principales: Sokolov, Mykyta, Nguyen, Van, Neumann, Ronald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519869/
https://www.ncbi.nlm.nih.gov/pubmed/26133243
http://dx.doi.org/10.3390/ijms160714737
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author Sokolov, Mykyta
Nguyen, Van
Neumann, Ronald
author_facet Sokolov, Mykyta
Nguyen, Van
Neumann, Ronald
author_sort Sokolov, Mykyta
collection PubMed
description The biological effects of low-dose ionizing radiation (LDIR) exposure in humans are not comprehensively understood, generating a high degree of controversy in published literature. The earliest stages of human development are known to be among the most sensitive to stress exposures, especially genotoxic stresses. However, the risks stemming from exposure to LDIR, particularly within the clinical diagnostic relevant dose range, have not been directly evaluated in human embryonic stem cells (hESCs). Here, we describe the dynamics of the whole genome transcriptional responses of different hESC lines to both LDIR and, as a reference, high-dose IR (HDIR). We found that even doses as low as 0.05 Gy could trigger statistically significant transient changes in a rather limited subset of genes in all hESCs lines examined. Gene expression signatures of hESCs exposed to IR appear to be highly dose-, time-, and cell line-dependent. We identified 50 genes constituting consensus gene expression signature as an early response to HDIR across all lines of hESC examined. We observed substantial differences in biological pathways affected by either LDIR or HDIR in hESCs, suggesting that the molecular mechanisms underpinning the responses of hESC may fundamentally differ depending on radiation doses.
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spelling pubmed-45198692015-08-03 Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure Sokolov, Mykyta Nguyen, Van Neumann, Ronald Int J Mol Sci Article The biological effects of low-dose ionizing radiation (LDIR) exposure in humans are not comprehensively understood, generating a high degree of controversy in published literature. The earliest stages of human development are known to be among the most sensitive to stress exposures, especially genotoxic stresses. However, the risks stemming from exposure to LDIR, particularly within the clinical diagnostic relevant dose range, have not been directly evaluated in human embryonic stem cells (hESCs). Here, we describe the dynamics of the whole genome transcriptional responses of different hESC lines to both LDIR and, as a reference, high-dose IR (HDIR). We found that even doses as low as 0.05 Gy could trigger statistically significant transient changes in a rather limited subset of genes in all hESCs lines examined. Gene expression signatures of hESCs exposed to IR appear to be highly dose-, time-, and cell line-dependent. We identified 50 genes constituting consensus gene expression signature as an early response to HDIR across all lines of hESC examined. We observed substantial differences in biological pathways affected by either LDIR or HDIR in hESCs, suggesting that the molecular mechanisms underpinning the responses of hESC may fundamentally differ depending on radiation doses. MDPI 2015-06-30 /pmc/articles/PMC4519869/ /pubmed/26133243 http://dx.doi.org/10.3390/ijms160714737 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sokolov, Mykyta
Nguyen, Van
Neumann, Ronald
Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure
title Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure
title_full Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure
title_fullStr Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure
title_full_unstemmed Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure
title_short Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure
title_sort comparative analysis of whole-genome gene expression changes in cultured human embryonic stem cells in response to low, clinical diagnostic relevant, and high doses of ionizing radiation exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519869/
https://www.ncbi.nlm.nih.gov/pubmed/26133243
http://dx.doi.org/10.3390/ijms160714737
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