TrajectoryGeometry suggests cell fate decisions can involve branches rather than bifurcations

Area of Science:

• Developmental Biology
• Computational Biology
• Systems Biology

Background:

• Cell differentiation is crucial for multicellular organisms.
• Current models assume linear trajectories with bifurcation points for cell fate decisions.
• Quantitative methods to test these models have been lacking.

Purpose of the Study:

• To develop and apply quantitative methods for analyzing cell differentiation trajectories.
• To test the prevailing model of bifurcating developmental pathways.
• To identify genes and pathways involved in cell fate determination.

Main Methods:

• Development of the R package TrajectoryGeometry.
• Application of TrajectoryGeometry to analyze published developmental data.
• Quantitative geometric analysis of cell differentiation paths.

Main Results:

• Identified instances where developmental pathways branch rather than bifurcate.
• Demonstrated that branching involves a secondary trajectory diverging from an initial one.
• Provided precise descriptions of genes and cellular pathways associated with these branching trajectories.

Conclusions:

• The traditional bifurcating model of cell differentiation may be less common than branching.
• Branching offers a new perspective on cell fate decisions and developmental processes.
• Branching may offer advantages from a control-theoretic perspective.