Lv Tianhang, Jiang Siyuan, Wang Xiaoshan, Hou Yong
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
BGI-Shenzhen, Shenzhen, 518083, China.
Heliyon. 2023 Jul 13;9(7):e18133. doi: 10.1016/j.heliyon.2023.e18133. eCollection 2023 Jul.
Mouse somatic cells can be reprogrammed into induced pluripotent stem cells through a highly heterogeneous process regulated by numerous biological factors, including adenosine-to-inosine (A-to-I) RNA editing. In this study, we analyzed A-to-I RNA editing sites using a single-cell RNA sequencing (scRNA-seq) dataset with high-depth and full-length coverage. Our method revealed that A-to-I RNA editing frequency varied widely at the single-cell level and underwent dynamic changes. We also found that A-to-I RNA editing level was correlated with the expression of the RNA editing enzyme ADAR1. The analysis combined with gene ontology (GO) enrichment revealed that ADAR1-dependent A-to-I editing may downregulate the expression levels of , , , and in the early stage, to inhibit the pathways of cellular response to interferon-beta and regulation of protein complex stability to promote mesenchymal-epithelial transition (MET). Notably, we identified a negative correlation between A-to-I RNA editing frequency and the expression of certain genes, such as , , , and .
小鼠体细胞可通过由众多生物因子（包括腺苷到次黄苷（A-to-I）RNA编辑）调控的高度异质过程重编程为诱导多能干细胞。在本研究中，我们使用具有高深度和全长覆盖的单细胞RNA测序（scRNA-seq）数据集分析了A-to-I RNA编辑位点。我们的方法揭示，A-to-I RNA编辑频率在单细胞水平上差异很大，并经历动态变化。我们还发现，A-to-I RNA编辑水平与RNA编辑酶ADAR1的表达相关。结合基因本体（GO）富集分析表明，ADAR1依赖性A-to-I编辑可能在早期下调 、 、 、 和 的表达水平，以抑制细胞对干扰素-β的反应途径和蛋白质复合体稳定性的调节，从而促进间充质-上皮转化（MET）。值得注意的是，我们发现A-to-I RNA编辑频率与某些基因（如 、 、 和 ）的表达呈负相关。
