Mechanistic elements and critical factors of cellular reprogramming revealed by stepwise global gene expression analyses
- Mechanistic elements and critical factors of cellular reprogramming revealed by stepwise global gene expression analyses
- 박성진; Hock Chuan Yeo; 강남영; 김한조; Joyce Lin; 하형호; Marc Vendrell; 이준석; Yogeswari Chandrana; 이동엽; 윤성욱; 장영태
- Issue Date
- STEM CELL RESEARCH
- VOL 12, NO 3, 730-741
- A better understanding of the cellular and molecular mechanisms involved in the reprogramming of somatic cells is essential for further improvement of induced pluripotent stem (iPS) cell technology. In this study, we enriched for cells actively undergoing reprogramming at different time points by sorting the cells stained with a stem cell-selective fluorescent chemical probe CDy1 for their global gene expression analysis. Day-to-day comparison of differentially expressed genes showed highly dynamic and transient gene expressions during reprogramming, which were largely distinct from those of fully-reprogrammed cells. An unbiased analysis of functional regulation indicated robust modulation of concurrent programs at critical junctures. Globally, transcriptional programs involved in cell proliferation, morphology and signal transduction were instantly triggered as early as 3 days-post-infection to prepare the cell for reprogramming but became somewhat muted in the final iPS cells. On the other hand, the highly coordinated metabolic reprogramming process was more gradually activated. Subsequent network analysis of differentially expressed genes indicated PDGF-BB as a core player in reprogramming which was verified by our gain- and loss-of-function experiments. As such, our study has revealed previously-unknown insights into the mechanisms of cellular reprogramming.
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