Profiling A-to-I RNA editing during mouse somatic reprogramming at the single-cell level

Tianhang Lv; Siyuan Jiang; Xiaoshan Wang; Yong Hou

doi:10.1016/j.heliyon.2023.e18133

Profiling A-to-I RNA editing during mouse somatic reprogramming at the single-cell level

Heliyon. 2023 Jul 13;9(7):e18133. doi: 10.1016/j.heliyon.2023.e18133. eCollection 2023 Jul.

Authors

Tianhang Lv^{1

2}, Siyuan Jiang^{1

2}, Xiaoshan Wang², Yong Hou^{1

2}

Affiliations

¹ College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
² BGI-Shenzhen, Shenzhen, 518083, China.

Abstract

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 Igtp, Irgm2, Mndal, Ifi202b, and Tapbp 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 Nras, Ube2l6, Zfp987, and Adsl.

Keywords: ADAR1; Mouse somatic reprogramming; Single-cell RNA editing.