Translational Landscape in Human Early Neural Fate Determination

Gene expression regulation in eukaryotes is a multi-level process, including transcription, mRNA translation, and protein turnover. Many studies have reported the sophisticated transcriptional regulations during neural development, but the global translational dynamics is still ambiguous. Here, we differentiated human embryonic stem cells (ESCs) into neural progenitor cells (NPCs) with high efficiency and performed ribosome sequencing and RNA sequencing on both ESCs and NPCs. Data analysis revealed that translational controls engaged in many critical pathways and contributed significantly to neural fate determination regulation. Furthermore, we showed that the sequence characteristics in the untranslated region (UTR) might regulate translation efficiency. Specifically, genes with short 5UTR and intense Kozak sequence are associated with high translation efficiency in human ESCs, while genes with long 3'UTR are related to high translation efficiency in NPCs. In addition, we identified four biasedly-used codons (GAC, GAT, AGA, and AGG) and dozens of short open reading frames during neural progenitor differentiation. Thus, our study reveals the translational landscape during early human neural differentiation and provides insights into the regulation of cell fate determination at the translational level. Overall design: We differentiated human embryonic stem cells (ESCs) into neural progenitor cells (NPCs) with high efficiency and performed ribosome sequencing and RNA sequencing on both ESCs and NPCs.