The origin of hematopoietic cell type diversity

Oncogene
Trang Hoang

Abstract

The hematopoietic system remains robust with regards to extrinsic perturbations, in sharp contrast with the stochastic behavior of hematopoeitic stem cells (HSCs) at the single cell level, suggesting that stability may be achieved within a stem cell system that undergoes constant self-renewal, commitment to differentiation and generates cell type diversification. Converging evidence at the interface of cellular, molecular and numerical studies suggests that diversity is generated by the chaotic dynamics of transcription factor networks within a cell and of the combination of growth factors and cytokines in the environment, both involving cooperation and competition. Current evidence indicates that HSCs are primed for multilineage gene expression. A subtle shift in transcription factor dosage is sufficient to perturb this equilibrium and to drive lineage commitment that involves a resolution of complexity at the molecular level and a transition towards less chaotic behavior. This dynamical instability establishes a state of responsiveness to extrinsic signals. Evolutionary conserved environmental cues that drive pattern formation or migratory behavior during embryonic development operate in the adult to influence the decision be...Continue Reading

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Citations

Nov 13, 2008·Cytotechnology·Tobias MayDagmar Wirth
Sep 20, 2005·Nature·Alejandro Colman-LernerRoger Brent
May 11, 2005·Nature Reviews. Genetics·Mads KaernJames J Collins
Jul 16, 2008·Tissue Engineering. Part a·Eric M Darling, Farshid Guilak
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May 2, 2006·Molecular and Cellular Biology·Nader OmidvarRichard L Darley
Mar 14, 2007·Genome Biology·Juan-Ramon Martinez-MoralesJoachim Wittbrodt
Mar 15, 2006·International Journal of Hematology·John E Dick, Tsvee Lapidot
Jan 31, 2008·Cells, Tissues, Organs·Michael A Rieger, Timm Schroeder
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Jun 17, 2006·The Journal of Gene Medicine·Christel KruegerChristian Berens
Nov 22, 2007·International Journal of Cancer. Journal International Du Cancer·Esko KankuriJozef Bizik

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