Mechanistic elements and critical factors of cellular reprogramming revealed by stepwise global gene expression analyses

Title
Mechanistic elements and critical factors of cellular reprogramming revealed by stepwise global gene expression analyses
Authors
박성진Hock Chuan Yeo강남영김한조Joyce Lin하형호Marc Vendrell이준석Yogeswari Chandrana이동엽윤성욱장영태
Issue Date
2014-05
Publisher
STEM CELL RESEARCH
Citation
VOL 12, NO 3, 730-741
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/47465
ISSN
18735061
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KIST Publication > Article
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