Combined single-cell profiling and functional analysis reveals the importance of pseudogenes in human early embryonic development

More and more studies have demonstrated that pseudogenes possess coding ability, and the functions of their transcripts in the development of diseases have been partially revealed. However, the role of pseudogenes in maintenance of normal physiological states and life activities has long been neglected. We identified pseudogenes that were dynamically expressed during human early embryogenesis, which showed different expression pattern from that of adult tissues. We explored the expression correlation between pseudogenes and the parent genes, part due to their shared gene regulatory elements or the potential regulation network between them. The essential role of three pseudogenes, PI4KAP1, TMED10P1 and FBXW4P1, in maintaining self-renewal of human embryonic stem cells was demonstrated. We further found that the three pseudogenes might perform their regulatory functions by binding to proteins or microRNAs. The pseudogene-related single-nucleotide polymorphisms were significantly associated with human congenital disease, further illustrating their importance during early embryonic development. Overall, this study is an excavation and exploration of functional pseudogenes during early human embryonic development, suggesting that pseudogenes are not only capable of being specifically activated in pathological states, but also play crucial functions in the maintenance of normal physiological states.