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During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
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Constructing maps between distinct cell fates and parametric conditions by systematic perturbations.

Ruoyu Tang1, Xinyu He1, Ruiqi Wang1,2

  • 1Department of Mathematics, Shanghai University, Shanghai 200444, China.

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Summary

This study introduces a computational method to map cell fate decisions to specific parameter conditions using systematic perturbations. This approach helps predict and control cell states during developmental processes.

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Area of Science:

  • Computational biology
  • Systems biology
  • Developmental biology

Background:

  • Cell fate transitions are fundamental to development, but understanding the underlying molecular mechanisms and parameter dependencies is challenging.
  • Traditional methods for analyzing biomolecular networks are limited by complexity and the need for precise parameter measurements.
  • Inferring parametric conditions that drive distinct cell fates through systematic perturbations requires further investigation.

Purpose of the Study:

  • To present a general computational method for constructing maps between cell fates and parametric conditions.
  • To demonstrate how systematic perturbations can reveal relationships between system parameters and cell fate decisions.
  • To provide a tool for predicting, manipulating, and controlling cell states during development.

Main Methods:

  • Integration of systematic perturbations, unsupervised clustering, principal component analysis, and fitting analysis.
  • Development of a method to construct maps between cell fates and parametric conditions without requiring accurate parameter measurements or bifurcation analysis.
  • Validation using model systems including toggle switch, inner cell mass, and epithelial mesenchymal transition.

Main Results:

  • Successfully constructed maps linking cell fates to parametric conditions across different model systems.
  • Demonstrated that system parameters encode essential information for cell fate decisions and transitions.
  • Showcased how systematic perturbations drive cell fate changes, enabling prediction and manipulation of cell states.
  • Highlighted the utility of the approach in understanding parameter combinations crucial for fate transitions.

Conclusions:

  • The developed computational method provides a powerful framework for understanding and controlling cell fate transitions.
  • The generated maps offer valuable insights into the parametric conditions governing cell fate decisions.
  • This approach can guide targeted interventions for realizing specific developmental outcomes, such as directional differentiation.