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

Sung-Jin Park, Hock Chuan Yeo, Nam-Young Kang, Hanjo Kim, Joyce Lin, Hyung-Ho Ha, Marc Vendrell, Jun-Seok Lee, Yogeswari Chandran, Dong-Yup Lee, Seong-Wook Yun, Young-Tae Chang

Research output: Contribution to journalArticlepeer-review

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. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Original languageEnglish
Pages (from-to)730-741
Number of pages12
JournalStem Cell Research
Volume12
Issue number3
DOIs
Publication statusPublished - May 2014

Keywords

  • PLURIPOTENT STEM-CELLS
  • SOMATIC-CELLS
  • GROWTH-FACTOR
  • SELF-RENEWAL
  • IPS CELLS
  • PATHWAY
  • SPHINGOSINE-1-PHOSPHATE
  • MAINTENANCE
  • PLATFORM
  • ROLES

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