Abstract:
:Differentiation from a multipotent stem or progenitor state to a mature cell is an essentially irreversible process. The associated changes in gene expression patterns exhibit time-directionality. This "arrow of time" in the collective change of gene expression across multiple stable gene expression patterns (attractors) is not explained by the regulated activation, the suppression of individual genes which are bidirectional molecular processes, or by the standard dynamical models of the underlying gene circuit which only account for local stability of attractors. To capture the global dynamics of this nonequilibrium system and gain insight in the time-asymmetry of state transitions, we computed the quasipotential landscape of the stochastic dynamics of a canonical gene circuit that governs branching cell fate commitment. The potential landscape reveals the global dynamics and permits the calculation of potential barriers between cell phenotypes imposed by the circuit architecture. The generic asymmetry of barrier heights indicates that the transition from the uncommitted multipotent state to differentiated states is inherently unidirectional. The model agrees with observations and predicts the extreme conditions for reprogramming cells back to the undifferentiated state.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Wang J,Xu L,Wang E,Huang Sdoi
10.1016/j.bpj.2010.03.058subject
Has Abstractpub_date
2010-07-07 00:00:00pages
29-39issue
1eissn
0006-3495issn
1542-0086pii
S0006-3495(10)00424-8journal_volume
99pub_type
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