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Reprogramming cell fates: reconciling rarity with robustness

Sui Huang1

  • 1Institute for Biocomplexity and Informatics, University of Calgary, Calgary, AB, Canada. Sui.huang@ucalgary.ca

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|March 26, 2009
PubMed

Insights

Induced pluripotent stem cell (iPS) reprogramming reveals fundamental cell fate regulation. A rugged epigenetic landscape explains why these rare events are robust, offering a new framework for understanding cell reprogramming.

Area of Science:

  • Cell Biology
  • Systems Biology
  • Developmental Biology

Background:

  • Cell reprogramming allows differentiated somatic cells to achieve a pluripotent stem cell phenotype.
  • The robustness of stem cell generation contrasts with the rarity of reprogramming events.
  • Existing paradigms do not fully explain this apparent paradox in cell fate regulation.

Purpose of the Study:

  • To provide a pedagogical primer on gene regulatory networks as dynamic systems.
  • To review recent insights into gene expression noise and cell fate determination.
  • To offer a formal framework for understanding the rarity and robustness of cell fate reprogramming.

Main Methods:

  • Exploration of gene regulatory network dynamics.
  • Analysis of gene expression noise.
  • Review of existing literature on cell fate determination and reprogramming.

Main Results:

  • The concept of a rugged "epigenetic landscape" with attractor states explains reprogramming rarity and robustness.
  • Gene regulatory network dynamics are key to understanding cell fate.
  • Cell fate determination is influenced by gene expression noise.

Conclusions:

  • Reprogramming events are rare yet robust due to the inherent dynamics of gene regulatory networks and the epigenetic landscape.
  • A formal framework integrating gene regulatory networks, noise, and epigenetic landscapes is crucial for understanding cell fate.
  • This work provides foundational insights into the fundamental principles of cell fate regulation and reprogramming.

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