Isotope Science Center, The University of Tokyo, Tokyo, Japan.
Reiwa Eye Clinic, Hatsukaichi, Hiroshima, Japan.
Sci Rep. 2023 Aug 9;13(1):12888. doi: 10.1038/s41598-023-40051-6.
The effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radiation and predicted their changes. Developing retinal cells generated from human induced pluripotent stem cells (iPSCs) were irradiated with either 30 or 180 mGy on days 4-5 of development for 24 h. Genome-wide gene expression was observed until day 35. A knowledge-based pathway analysis algorithm revealed fluctuations in Rho signaling and many other pathways. After a month, the levels of an essential transcription factor of eye development, the proportion of paired box 6 (PAX6)-positive cells, and the proportion of retinal ganglion cell (RGC)-specific transcription factor POU class 4 homeobox 2 (POU4F2)-positive cells increased with 30 mGy of irradiation. In contrast, they decreased after 180 mGy of irradiation. Activation of the "development of neurons" pathway after 180 mGy indicated the dedifferentiation and development of other neural cells. Fluctuating effects after low-dose radiation exposure suggest that developing retinal cells employ hormesis and dedifferentiation mechanisms in response to stress.
低剂量辐射对未分化细胞的影响具有重要意义。然而，其对发育中的视网膜细胞的影响尚不清楚。在这里，我们分析了含有未成熟人视网膜细胞的神经元类器官在低剂量辐射下的基因表达特征，并预测了它们的变化。在发育的第 4-5 天，用人诱导多能干细胞（iPSC）产生的发育中的视网膜细胞分别用 30 或 180 mGy 照射 24 小时。直到第 35 天观察到全基因组基因表达。基于知识的途径分析算法揭示了 Rho 信号和许多其他途径的波动。一个月后，眼发育的关键转录因子的水平，即配对盒 6（PAX6）阳性细胞的比例，以及视网膜神经节细胞（RGC）特异性转录因子 POU 类 4 同源框 2（POU4F2）阳性细胞的比例，随着 30 mGy 的照射而增加。相比之下，在 180 mGy 照射后，它们减少了。在 180 mGy 照射后，“神经元发育”途径的激活表明其他神经细胞的去分化和发育。低剂量辐射暴露后的波动效应表明，发育中的视网膜细胞可能采用适应原性和去分化机制来应对应激。
