Cell fates as high-dimensional attractor states of a complex gene regulatory network

Phys Rev Lett. 2005 Apr 1;94(12):128701. doi: 10.1103/PhysRevLett.94.128701. Epub 2005 Apr 1.

Abstract

Cells in multicellular organisms switch between distinct cell fates, such as proliferation or differentiation into specialized cell types. Genome-wide gene regulatory networks govern this behavior. Theoretical studies of complex networks suggest that they can exhibit ordered (stable) dynamics, raising the possibility that cell fates may represent high-dimensional attractor states. We used gene expression profiling to show that trajectories of neutrophil differentiation converge to a common state from different directions of a 2773-dimensional gene expression state space, providing the first experimental evidence for a high-dimensional stable attractor that represents a distinct cellular phenotype.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Dimethyl Sulfoxide / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • HL-60 Cells
  • Humans
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tretinoin / pharmacology

Substances

  • RNA, Messenger
  • Tretinoin
  • Dimethyl Sulfoxide