Cell fates as high-dimensional attractor states of a complex gene regulatory network.
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.
Huang
Sui
S
Vascular Biology Program, Departments of Pathology & Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. sui.huang@childrens.harvard.edu
Eichler
Gabriel
G
Bar-Yam
Yaneer
Y
Ingber
Donald E
DE
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D012333:RNA, Messenger; D014212:Tretinoin; D004121:Dimethyl Sulfoxide