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Related Concept Videos

Maintenance of the ES Cell State01:14

Maintenance of the ES Cell State

The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...

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Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
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Nanog-dependent feedback loops regulate murine embryonic stem cell heterogeneity.

Ben D MacArthur1, Ana Sevilla, Michel Lenz

  • 1Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO17 1BJ, UK.

Nature Cell Biology
|October 30, 2012
PubMed
Summary

Mouse embryonic stem cell identity relies on Nanog feedback loops. Loss of Nanog initially causes reversible changes, but prolonged absence leads to irreversible fate decisions and reduced population variability.

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Area of Science:

  • Stem cell biology
  • Developmental biology
  • Genetics

Background:

  • Embryonic stem (ES) cell identity is regulated by key factors like Nanog.
  • Expression fluctuations of these regulators occur at the single-cell level.
  • The molecular basis for these fluctuations remains unclear.

Purpose of the Study:

  • To investigate the molecular basis of expression changes during Nanog downregulation in mouse ES cells.
  • To understand the role of Nanog in maintaining ES cell identity and regulatory network stability.

Main Methods:

  • Genetic complementation strategy to study Nanog downregulation.
  • High-throughput single-cell transcriptional profiling.
  • Mathematical modeling of gene expression dynamics.

Main Results:

  • Early molecular changes following Nanog loss are stochastic and reversible.
  • Nanog loss disrupts the self-sustaining feedback structure of the ES cell regulatory network.
  • Prolonged Nanog absence leads to consolidation of changes into committed fate decisions.
  • Exogenous regulation of Nanog feedback mechanisms promotes ES cell population homogeneity.

Conclusions:

  • Nanog-dependent feedback loops are crucial for controlling ES cell fate decisions.
  • These feedback loops also play a significant role in regulating ES cell population variability.
  • Understanding Nanog's role is key to controlling stem cell pluripotency and differentiation.