Stem cell decision making and critical-like exploratory networks

By jpeza - Posted on 09 Julio 2009

Fecha Publicación: 
1 Ene 2009
Nombre de Revista: 
Datos del paper
Autor Principal: 
Julianne D. Halley
Página Inicial: 
Página Final: 

A sound theoretical or conceptual model of gene regulatory processes that control stem cell fate is still lacking,

compromising our ability to manipulate stem cells for therapeutic benefit. The complexity of the regulatory and signaling

pathways limits development of useful, predictive models that employ solely reductionist methods using molecular

components. However, there is clear evidence from other complex systems that coarse-grained or mesoscale models can yield

useful insights and provide workable models for the prediction of some emergent properties such as cell phenotype. We present

such a coarse-grained model of stem cell decision making, utilizing the concept of self-organized criticality, which is an order

that propagates in some nonequilibrium systems. The model proposes that stochastic gene expression within a stem cell gene

regulatory network self-organizes to a critical-like state, characterized by cascades of gene expression that prime various

transcriptional programs associated with different cell fates. This diversity of cell fate options is reduced during the

decision-making process, which involves a supercritical connectivity in the gene regulatory network as a stem cell leaves its

niche microenvironment and an overall increase in transcription occurs. As modules of genes that correspond to specific cell

fates approach their critical points, competitive interactions occur between them that are influenced by prevailing

microenvironmental conditions. The conceptual model incorporates both intrinsic and extrinsic factors governing stem cell fate

and provides a logical pathway to the development of a computational model. We further suggest that rapid self-organized

criticality, rather than self-organized criticality, best describes the mesoscale organization of gene regulatory networks.

© 2009 Elsevier B.V. All rights reserved.

Dirección del Autor: 

a CSIRO Molecular and Health Technologies, Private Bag 10, Clayton South MDC 3169, Australia

b Monash University, School of Chemistry, Victoria, Australia

c SciMetrics, Victoria, Australia

gene regulatory ; stem cell ; coarse-grained ; mesoscale models

Frank R. Burden a,b,c, David A. Winkler a,b

[file] Stem_Cell_Research_2009_vol 2_pp 165-177.pdf546.74 KB