A team of scientists announced a critical step on the path of realizing the promise of embryonic stem (ES) cells for medicine. As described in the April 21 issue of Cell, the researchers have discovered unique molecular imprints coupled to DNA in mouse ES cells that help explain the cells' rare ability to form almost any body cell type. These imprints, or "signatures," appear near the master genes that control embryonic development and probably coordinate their activity in the early stages of cell differentiation. Not only do these findings help to unlock the basis for ES cells' seemingly unlimited potential, they also suggest ways to understand why ordinary cells are so limited in their abilities to repair or replace damaged cells.
"This is an entirely new and unexpected discovery," said Brad Bernstein, lead author of the study, assistant professor at Massachusetts General Hospital and Harvard Medical School, and a researcher in the Chemical Biology program at the Broad Institute. "It has allowed us to glimpse the molecular strategies that cells use to maintain an almost infinite potential, which will have important applications to our understanding of normal biology and disease."
Chromatin-the protein scaffold that surrounds DNA - acts not only as a support for the double helix but also as a kind of gene "gatekeeper." It accomplishes the latter task by selecting which genes to make active or inactive in a cell, based on the nearby chemical tags joined to its backbone. By examining the chromatin in mouse ES cells across the genome, the scientists discovered an unusual pair of overlapping molecular tags in the chromatin structure, which together comprise what they called a "bivalent domain," reflecting the dual nature of its design. These domains reside in the sections of chromatin that control the most evolutionarily conserved portions of DNA, particularly the key regulatory genes for embryonic development.
"These signatures appear frequently in ES cells, but largely disappear once the cells choose a direction developmentally," said Bernstein. "This suggests they play a significant role in regulating the cells' unique plasticity."