Molecular Insights into Reprogramming-Initiation Events Mediated by the OSKM Gene Regulatory Network Initiation Events during OSKM-Based Reprogramming
2011

Understanding Early Events in Reprogramming Cells to Induced Pluripotent Stem Cells

publication 10 minutes Evidence: moderate

Author Information

Author(s): Mah Nancy, Wang Ying, Liao Mei-Chih, Prigione Alessandro, Jozefczuk Justyna, Lichtner Björn, Wolfrum Katharina, Haltmeier Manuela, Flöttmann Max, Schaefer Martin, Hahn Alexander, Mrowka Ralf, Klipp Edda, Andrade-Navarro Miguel A., Adjaye James

Primary Institution: Max Delbrück Center for Molecular Medicine, Berlin, Germany

Hypothesis

What are the early mechanisms underlying the induction of pluripotency in somatic cells?

Conclusion

The study suggests that the viral response during reprogramming can hinder efficiency, but specific strategies may improve the process.

Supporting Evidence

  • Viral transduction leads to an innate immune response that reduces reprogramming efficiency.
  • Nucleofection of OSKM plasmids does not elicit the same cellular stress as viral transduction.
  • Specific strategies can enhance reprogramming efficiency by targeting immune responses and selecting for pluripotency markers.
  • Transcriptional profiles show a shift from fibroblast-like to pluripotent-like over time.
  • Activation of p53 and ROS production are significant early events in the reprogramming process.
  • Gene expression changes indicate a transient immune response that may hinder reprogramming.
  • Pluripotency-associated genes are gradually activated during the reprogramming process.

Takeaway

Scientists are trying to turn regular cells into special stem cells, but the way they do it can cause problems. They found ways to make it work better.

Methodology

The study analyzed transcriptional profiles at 24, 48, and 72 hours post-transduction of OSKM into human foreskin fibroblasts using microarray technology.

Potential Biases

Potential bias due to the reliance on viral transduction methods which may introduce variability.

Limitations

The study primarily focuses on early transcriptional changes and does not address long-term effects of reprogramming.

Participant Demographics

Human foreskin fibroblasts were used as the source of somatic cells.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0024351

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