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TrajectoryGeometry suggests cell fate decisions can involve branches rather than bifurcations.

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posted on 2024-10-14, 10:51 authored by Anna Laddach, Vassilis Pachnis, Michael Shapiro
Differentiation of multipotential progenitor cells is a key process in the development of any multi-cellular organism and often continues throughout its life. It is often assumed that a bi-potential progenitor develops along a (relatively) straight trajectory until it reaches a decision point where the trajectory bifurcates. At this point one of two directions is chosen, each direction representing the unfolding of a new transcriptional programme. However, we have lacked quantitative means for testing this model. Accordingly, we have developed the R package TrajectoryGeometry. Applying this to published data we find several examples where, rather than bifurcate, developmental pathways branch. That is, the bipotential progenitor develops along a relatively straight trajectory leading to one of its potential fates. A second relatively straight trajectory branches off from this towards the other potential fate. In this sense only cells that branch off to follow the second trajectory make a 'decision'. Our methods give precise descriptions of the genes and cellular pathways involved in these trajectories. We speculate that branching may be the more common behaviour and may have advantages from a control-theoretic viewpoint.

Funding

Crick (Grant ID: CC2117, Grant title: Pachnis CC2117) Wellcome Trust (Grant ID: 225712/Z/22/Z, Grant title: WT 225712/Z/22/Z) Wellcome Trust (Grant ID: 212300/Z/18/Z, Grant title: WT 212300/Z/18/Z)

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