Forced Expression of Brg1 Tips the Balance in Stem Cell Cycles

Newswise — Scientists have known that it takes combinations of chromatin remodeling factors to keep the processes of self-renewal, proliferation and differentiation of stem cells in proper balance. Now, researchers from the Sbarro Institute of Cancer Research and Molecular Medicine and Second University of Naples in Naples, Italy, have discovered that forced expression of chromatin remodeling factor Brg1 induces cell cycle arrest, death and deterioration in mesenchymal stem cells (MSCs), upsetting this delicate harmony.

The researchers report their findings, "Brg1 chromatin remodeling factor is involved in cell growth arrest, apoptosis and senescence of rat mesenchymal stem cells" in the August 15 issue Journal of Cell Science (J Cell Sci.2007; 120: 2904-2911; http://jcs.biologists.org/cgi/content/abstract/120/16/2904).

When researchers examined the results of ectopic expression of Brg1 at the molecular level, they found that it upregulates, or increases, activation in Rb- and p53-related pathways. Unraveling the molecular mechanisms behind these observations, investigators find that the apoptosis, or cell death, that occurs is mediated by p53, while both Rb-and p53-related pathways are required for the observed cell cycle arrest and senescence.

The study also shows that the forced expression of Brg1 is linked to the differentiation of adipoctyes or fat cells " although the authors note that " unlike other ATP dependent chromatin-remodeling factors " Brg1 does not appear to directly regulate access to promoters of genes that encode transcription factors. Rather, it promotes differentiation in adipocytes when other, extrinsic factors that promote adipogenesis are added to the culture medium.

"While some chromatin remodeling factors promote stem cell self-renewal and conservation of an uncommitted state," says Umberto Galderisi, the lead author of the study, "Others appear to cause an escape from 'stemness' and induction of differentiation along with senescence and cell death phenomena."

About the Sbarro Health Research Organization

SHRO (http://www.shro.org) SHRO funds the Sbarro Institute for Cancer Research and Molecular Therapeutics located at Temple University in Philadelphia, PA as well as a lab in Siena, Italy located at the University of Siena.