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Cell Cycle Heterogeneity Can Generate Robust Cell Type Proportioning.

Nicole Gruenheit1, Katie Parkinson2, Christopher A Brimson3

  • 1Centre for Life's Origins and Evolution, Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK; Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.

Developmental Cell
|November 27, 2018
PubMed
Summary
This summary is machine-generated.

Cell cycle variation in developing cells helps determine cell fate, ensuring consistent proportions of cell types. This heterogeneity is crucial for robust developmental outcomes.

Keywords:
Dictyosteliumcell cyclecell fateheterogeneitylineage primingoscillatorsingle-cell sequencing

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Area of Science:

  • Developmental biology
  • Cellular heterogeneity
  • Quantitative biology

Background:

  • Cell-cell heterogeneity is vital for lineage choices in embryonic development.
  • The origins of this heterogeneity and its control for reproducible cell type proportions remain unclear.

Purpose of the Study:

  • To investigate the role of cell cycle heterogeneity in generating robust cell fate proportioning.
  • To understand how intrinsic and extrinsic variations contribute to developmental reproducibility.

Main Methods:

  • Utilized experimentation and mathematical modeling in Dictyostelium discoideum.
  • Quantitatively linked cell cycle position to differentiation signal responsiveness.
  • Analyzed intrinsic variation in cell cycle length and extrinsic perturbations.

Main Results:

  • Established a quantitative link between cell cycle position and differentiation cue responsiveness.
  • Demonstrated that intrinsic cell cycle length variation leads to random cell cycle distribution at development onset.
  • Showed that extrinsic perturbations to cell cycle heterogeneity are buffered by compensatory changes in signal responsiveness.

Conclusions:

  • Population-level cell cycle heterogeneity can be optimized for robust cell fate proportioning.
  • Intrinsic variation ensures proper cell distribution for developmental signaling.
  • Developmental processes exhibit buffering mechanisms against extrinsic variations in heterogeneity.