Researchers Make Stem Cell Find

Last Friday, a team of researchers primarily from the Broad Institute of Harvard and MIT published a report that may bring scientists much closer to finally understanding how embryonic stem (ES) cells differentiate themselves, with potential implications for future regenerative therapies.

Every cell in the human body contains the same genes, but the cells in a particular type of tissue will only have the master regulatory genes associated with that tissue type activated. For example, if a cell is a muscle tissue cell, it will only have the master regulatory genes for muscle tissue activated and will have other master regulatory genes deactivated. ES cells have the potential to become any other type of tissue cell, but how they do so is not clear and is essential if treatments are to be developed from research.

This process of activating master regulatory genes is facilitated by chromatin, a histone protein structure that contains a cell’s DNA. If there is a methyl group anchored in a certain place on one histone protein, the gene nearby is activated (known as the K4 state). Conversely, if the methyl group attaches itself to another part of the protein, the gene is deactivated (known as the K27 state).

The study of mouse ES cells, published in the April 21 issue of Cell, is revolutionary because it overturns previous conventional wisdom regarding the K4 and K27 states.

“What we found was that [mouse ES cells] have a chromatin signature that other cells don’t have—they have both a K4 and K27 signature, which was surprising because we thought they were mutually exclusive,” said Bradley E. Bernstein, assistant professor of pathology at Massachusetts General Hospital and Harvard Medical School, and the lead author of the study.

Since the master regulatory genes near the simultaneous K4 and K27 states are by and large silent, it appears that K27 dominates K4 when both are simultaneously present. However, the presence of K4 indicates that these genes may later be activated.

“For genes, this is equivalent to resting one finger on the trigger,” said Stuart L. Schreiber, Loeb professor and chair of the department of chemistry and chemical biology and an author of the study, in a statement.

“This approach could be a key strategy for keeping crucial genes quiet, but primed for when they will be most needed.”

While the discovery does not in and of itself explain how an ES cell differentiates itself, it provides hints for the mechanisms that might guide this process.

Moreover, the discovery of these “bivalent chromatin structures” may have important implications for branches other than stem cell medicine as well.

“I think that understanding how these sorts of bivalent structures contribute to the unique potential of these kind of cells has important implications not only for stem cell biology and regenerative medicine, but for cancer and other diseases where chromatin misregulation or deregulation is involved,” Bernstein said.