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Multi-omics approach reveals posttranscriptionally regulated genes are essential for human pluripotent stem cells. 2022

Mio Iwasaki, and Yuka Kawahara, and Chikako Okubo, and Tatsuya Yamakawa, and Michiko Nakamura, and Tsuyoshi Tabata, and Yohei Nishi, and Megumi Narita, and Akira Ohta, and Hirohide Saito, and Takuya Yamamoto, and Masato Nakagawa, and Shinya Yamanaka, and Kazutoshi Takahashi

Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.

The effects of transcription factors on the maintenance and differentiation of human-induced or embryonic pluripotent stem cells (iPSCs/ESCs) have been well studied. However, the importance of posttranscriptional regulatory mechanisms, which cause the quantitative dissociation of mRNA and protein expression, has not been explored in detail. Here, by combining transcriptome and proteome profiling, we identified 228 posttranscriptionally regulated genes with strict upregulation of the protein level in iPSCs/ESCs. Among them, we found 84 genes were vital for the survival of iPSCs and HDFs, including 20 genes that were specifically necessary for iPSC survival. These 20 proteins were upregulated only in iPSCs/ESCs and not in differentiated cells derived from the three germ layers. Although there are still unknown mechanisms that downregulate protein levels in HDFs, these results reveal that posttranscriptionally regulated genes have a crucial role in iPSC survival.