Atlas of subcellular RNA localization in human embryonic stem cells and its flow during differentiation

The distribution of RNA in human embryonic stem cells (hESC) and the function of RNA localization in maintaining hESC pluripotency and differentiation are currently unknown. Here, by isolating five subcellular components of hESCs and differentiated cells, we uncovered the global subcellular RNA localization in hESC. For protein-coding mRNA, different transcripts of the same gene exhibit an “isoform switch” between subcellular components, which is regulated by localization cis-elements in their variable regions. For noncoding RNA, multiple sequence features such as polyA tail, length, and GC content jointly regulate their subcellular localization. In addition, we found that some developmental genes can be transcribed in advance and confined to chromatin in undifferentiated hESCs. Finally, we revealed significant changes in overall RNA distribution, mapped RNA dynamic localization atlas, and characterized different dynamic RNA localization patterns during hESC differentiation into mesoderm. The multiple RNA localization patterns we revealed will provide some new enlightenment for hESC stemness maintenance and differentiation. Overall design: RNA localization profiling of RNA-seq data of subcellular components for hESCs and differentiated cells (Day3 and Day5).