Cell Type– and Age-Specific Expression of lncRNAs across Kidney Cell Types

Abstract

Key Points We constructed a single-cell long noncoding RNA atlas of various tissues, including normal and aged kidneys.We identified age- and cell type–specific expression changes of long noncoding RNAs in kidney cells. Background Accumulated evidence demonstrates that long noncoding RNAs (lncRNAs) regulate cell differentiation and homeostasis, influencing kidney aging and disease. Despite their versatility, the function of lncRNA remains poorly understood because of the lack of a reference map of lncRNA transcriptome in various cell types. Methods In this study, we used a targeted single-cell RNA sequencing method to enrich and characterize lncRNAs in individual cells. We applied this method to various mouse tissues, including normal and aged kidneys. Results Through tissue-specific clustering analysis, we identified cell type–specific lncRNAs that showed a high correlation with known cell-type marker genes. Furthermore, we constructed gene regulatory networks to explore the functional roles of differentially expressed lncRNAs in each cell type. In the kidney, we observed dynamic expression changes of lncRNAs during aging, with specific changes in glomerular cells. These cell type– and age-specific expression patterns of lncRNAs suggest that lncRNAs may have a potential role in regulating cellular processes, such as immune response and energy metabolism, during kidney aging. Conclusions Our study sheds light on the comprehensive landscape of lncRNA expression and function and provides a valuable resource for future analysis of lncRNAs (https://gist-fgl.github.io/sc-lncrna-atlas/).