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

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

doi:10.1016/j.isci.2022.104289

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

iScience. 2022 Apr 25;25(5):104289. doi: 10.1016/j.isci.2022.104289. eCollection 2022 May 20.

Authors

Mio Iwasaki¹, Yuka Kawahara¹, Chikako Okubo¹, Tatsuya Yamakawa¹, Michiko Nakamura¹, Tsuyoshi Tabata¹, Yohei Nishi^{1

2}, Megumi Narita¹, Akira Ohta¹, Hirohide Saito¹, Takuya Yamamoto^{1

3

4}, Masato Nakagawa¹, Shinya Yamanaka^{1

5

6}, Kazutoshi Takahashi¹

Affiliations

¹ Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
² iPSC-Based Drug Discovery and Development Team, RIKEN Bio Resource Research Center (BRC), Kyoto, Japan.
³ Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501, Japan.
⁴ Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Tokyo, Japan.
⁵ Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
⁶ Department of Anatomy, University of California, San Francisco, CA 94143, USA.

Abstract

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.

Keywords: Biological sciences; Omics; Stem cells research.