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Stem Cells' "Suspended" State Preserved by Key Step, Scientists Report
Date:7/8/2009

new research, conducted on mouse embryo cells, revealed that a gene known as Chd1 loosens the packaging that normally protects DNA in the cell nucleus. This step, known as chromatin remodeling, allows the cell's protein-making machinery to gain access to the DNA and transform progenitor cells into specialized cells and tissue, such as neurons, muscle and bone.

A number of genes are known to trigger chromatin remodeling, allowing small sections of DNA to become accessible in order to make specific proteins. Chd1 is the first gene found to regulate a "global" loosening of the DNA in embryonic stem cells, the scientists report. The global condition sets the stage for turning on many different genes to make a broad range of specialized cells.

"Embryonic stem cells are characterized by this open state, but, up to now, we didn't know the mechanisms that maintain this state, or even if it is necessary for the full stem cell potential," said Alexandre Gaspar-Maia, lead author of the paper.

"We found that Chd1 is critical for both, and for allowing an efficient reprogramming. Chd1 is important for allowing the normal differentiation process, and it is essential for playing the 'differentiation tape' backwards - bringing differentiated cells back to pluripotency."

Gaspar-Maia is a graduate student (from the PhD Program in Experimental Biology and Biomedicine, at the University of Coimbra, Portugal) in the lab of senior author Miguel Ramalho-Santos, PhD, of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

The scientists discovered the pivotal role of Chd1 by using the powerful technique of RNA interference, or RNAi, to screen this gene and 40 other candidate genes. (RNAi is a naturally occurring process in which small RNAs bind to other RNAs to increase or decrease their activity.) In this case, the scientists used the technique to silence Chd1. When they d
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