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.

中文翻译：

---

人胚干细胞神经分化过程中电离辐射对转录组的影响。

人类胚胎的大脑发育对电离辐射高度敏感。但是，由于有限的实验数据，无法获得有关这种敏感性机制的详细信息。在这项研究中，人类胚胎干细胞（hESCs）向神经谱系的分化被用作早期胚胎脑发育的模型，以评估暴露于低剂量（17 mGy）和高剂量（572 mGy）的辐射对基因表达的影响。在对照和辐照样品的三个时间点，在神经分化过程中使用RNA测序对转录组进行评估。第一个时间点是细胞仍然是多能的（第0天），第二个时间点是在类胚体形成阶段（第6天），第三个也是最后一个时间点是在神经玫瑰花结形成阶段（第6天）。 10）。转录组的分析揭示了对照细胞和照射细胞中的神经分化。低剂量照射在任何时间点都不会导致基因表达的变化，而高剂量照射会在第6天和第10天导致一些主要的神经分化标记物下调。基因本体分析表明，与神经系统发育相关的途径神经元的发生和神经元的产生受到的影响最大。神经元发育这类关键调节因子如NEUROG1，ARX，ASCL1，RFX4和INSM1的表达降低了两倍以上。总之，hESCs对17 mGy低剂量辐射的耐受性良好，而对572 mGy暴露则显着影响了它们向神经元谱系的遗传重编程。低剂量照射在任何时间点都不会导致基因表达的变化，而高剂量照射会在第6天和第10天导致一些主要的神经分化标记物下调。基因本体分析表明，与神经系统发育相关的途径神经元的产生和神经元的生成受到的影响最大。神经元发育这类关键调节因子如NEUROG1，ARX，ASCL1，RFX4和INSM1的表达降低了两倍以上。总之，hESCs对17 mGy低剂量辐射的耐受性良好，而对572 mGy暴露则显着影响了它们向神经元谱系的遗传重编程。低剂量照射在任何时间点都不会导致基因表达的变化，而高剂量照射会在第6天和第10天导致一些主要的神经分化标记物下调。基因本体分析表明，与神经系统发育相关的途径神经元的发生和神经元的产生受到的影响最大。神经元发育这类关键调节因子如NEUROG1，ARX，ASCL1，RFX4和INSM1的表达降低了两倍以上。总之，hESCs对17 mGy低剂量辐射的耐受性良好，而对572 mGy暴露则显着影响了它们向神经元谱系的遗传重编程。而大剂量照射则在第6天和第10天导致一些主要的神经分化标志物下调。基因本体分析表明，与神经系统发育，神经发生和神经元生成相关的途径受影响最大。神经元发育这类关键调节因子如NEUROG1，ARX，ASCL1，RFX4和INSM1的表达降低了两倍以上。总之，hESCs对17 mGy低剂量辐射的耐受性良好，而对572 mGy暴露则显着影响了它们向神经元谱系的遗传重编程。而大剂量照射则在第6天和第10天导致一些主要的神经分化标志物下调。基因本体分析表明，与神经系统发育，神经发生和神经元生成相关的途径受影响最大。神经元发育这类关键调节因子如NEUROG1，ARX，ASCL1，RFX4和INSM1的表达降低了两倍以上。总之，hESCs对17 mGy低剂量辐射的耐受性良好，而对572 mGy暴露则显着影响了它们向神经元谱系的遗传重编程。RFX4和INSM1减少了两倍多。总之，hESCs对17 mGy低剂量辐射的耐受性良好，而对572 mGy暴露则显着影响了它们向神经元谱系的遗传重编程。RFX4和INSM1减少了两倍多。总之，hESCs对17 mGy低剂量辐射的耐受性良好，而对572 mGy的辐射显着影响了它们向神经元谱系的遗传重编程。