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Epigenetics of reprogramming to induced pluripotency.
Bernadett Papp1, Kathrin Plath
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell
|March 19, 2013
Summary
Reprogramming cells into induced pluripotent stem cells (iPSCs) involves stepwise changes. Early epigenetic priming is crucial for later pluripotency, but X chromosome instability in human iPSCs needs attention.
Area of Science:
- Stem cell biology
- Epigenetics
- Cellular reprogramming
Background:
- Induced pluripotent stem cells (iPSCs) are generated through cellular reprogramming.
- Reprogramming is a stepwise process involving changes in transcription and chromatin states.
- Epigenetic modifications play a critical role in the efficiency and outcome of reprogramming.
Purpose of the Study:
- To elucidate the stepwise mechanisms of cellular reprogramming into iPSCs.
- To highlight the importance of early epigenetic events in pluripotency induction.
- To discuss the influence of reprogramming factors and extracellular conditions on the process.
Main Methods:
- Characterization of reprogramming factor binding and transcription dynamics.
- Analysis of changing chromatin states during reprogramming.
- Investigation of epigenetic priming events.
Main Results:
- Reprogramming factor binding, transcription, and chromatin modifications occur sequentially.
- Early epigenetic priming events are critical for successful pluripotency induction.
- Reprogramming factor levels, stoichiometry, and extracellular conditions significantly influence reprogramming outcomes.
- An epigenetic instability of the X chromosome in human iPSCs has been identified.
Conclusions:
- Understanding the stepwise nature of reprogramming, including epigenetic dynamics, is key to improving iPSC applications.
- Rational design of novel reprogramming factor cocktails is enabled by recent progress.
- The discovered epigenetic instability of the X chromosome in human iPSCs requires careful consideration for future research and therapeutic use.
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