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. 2010 May 25;8(5):e1000380.
doi: 10.1371/journal.pbio.1000380.

Cell lineage determination in state space: a systems view brings flexibility to dogmatic canonical rules

Sui Huang  1
Affiliations

Cell lineage determination in state space: a systems view brings flexibility to dogmatic canonical rules

Sui Huang. PLoS Biol. .
No abstract available

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Conflict of interest statement

The author has declared that no competing interests exist.

Figures

Figure 1
Figure 1. Fundamental principles of high-dimensional dynamical systems that may explain the coordinated change of gene expression during cell fate commitment and phenotype change and integrates chance and necessity.
(A) Basic concepts. The “cube” represents a three-dimensional state space (describing a three-gene system (genes A, B, and C) with their expression levels (xA, xB, and xC) as axes. A state S is a point in state space (blue ball). When gene expression pattern changes, the state moves along a trajectory. If gene B, which suppresses gene C, increases its expression xB, then the point S will move in the direction of the axis of increasing xB and at the same time, by necessity, of decreasing xC. (B) Application of state space and cell state concepts to a population of cells represented by a “cloud” of states. The interaction between the genes (state space dimensions) prevents the hypothetical even dispersion into the entire state space, instead allowing cells to occupy only predestined regions (cell type attractors) by following the trajectories (red). The mutual inhibition of xB and xC, for instance, pushes cells away towards an [xB≫xC] and an [xB≪xC] attractor. Yellow double arrow indicates the trajectory separation. For details see text. The insets at the bottom represent a histogram as typically observed in flow cytometry, which represents a projection of the state space for X B and the quasi-potential landscape (schematically) along X B. Note that because this is a non-integrable, non-conservative system, the elevation of the landscape does not represent true potential energy. (C) Example of a typical gene regulatory circuit of two mutually inhibiting and self-activating genes B and C (for instance Gata6 and Nanog) that establishes a metastable bipotent state xB≈xC that can differentiate into either one of the two committed lineage attractors, [xB≫xC] and [xB≪xC].
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  • PLoS Biol. 8:e1000379.

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