Open AccessEffect of Ionizing Radiation on Transcriptome during Neural Differentiation of Human Embryonic Stem Cells
Author(s) -
Burk W. Loeliger,
Christine Hanu,
Irina V. Panyutin,
Roberto MaassMoreno,
Paul Wakim,
William F. Pritchard,
Ronald D. Neumann,
Igor G. Panyutin
Publication year - 2020
Publication title -
radiation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 124
eISSN - 1938-5404
pISSN - 0033-7587
DOI - 10.1667/rr15535.1
Subject(s) - embryonic stem cell , biology , transcriptome , embryoid body , neurogenesis , embryogenesis , neural stem cell , microbiology and biotechnology , induced pluripotent stem cell , neural development , stem cell , gene expression , embryo , genetics , gene
Human embryonic brain development is highly sensitive to ionizing radiation. However, detailed information on the mechanisms of this sensitivity is not available due to limited experimental data. In this study, differentiation of human embryonic stem cells (hESCs) to neural lineages was used as a model for early embryonic brain development to assess the effect of exposure to low (17 mGy) and high (572 mGy) doses of radiation on gene expression. Transcriptomes were assessed using RNA sequencing during neural differentiation at three time points in control and irradiated samples. The first time point was when the cells were still pluripotent (day 0), the second time point was during the stage of embryoid body formation (day 6), and the third and final time point was during the stage of neural rosette formation (day 10). Analysis of the transcriptomes revealed neurodifferentiation in both the control and irradiated cells. Low-dose irradiation did not result in changes in gene expression at any of the time points, whereas high-dose irradiation resulted in downregulation of some major neurodifferentiation markers on days 6 and 10. Gene ontology analysis showed that pathways related to nervous system development, neurogenesis and generation of neurons were among the most affected. Expression of such key regulators of neuronal development as NEUROG1, ARX, ASCL1, RFX4 and INSM1 was reduced more than twofold. In conclusion, exposure to a 17 mGy low dose of radiation was well tolerated by hESCs while exposure to 572 mGy significantly affected their genetic reprogramming into neuronal lineages.