Putting microRNAs on the stem cell map( CAMBRIDGE Mass. (August 7 2008) E...),Health

CAMBRIDGE, Mass. (August 7, 2008) Embryonic stem cells are always facing a choiceeither to self-renew or begin morphing into another type of cell altogether.

It's a tricky choice, governed by complex gene regulatory circuitry driven by a handful of key regulators known as "master transcription factors," proteins that switch gene expression on or off.

In the past few years, scientists in the lab of Whitehead Member Richard Young and their colleagues have mapped out key parts of this regulatory circuitry, but the genes that produce the tiny snippets of RNA known as microRNAs have until now been a missing piece of the map. Since microRNAs are a second set of regulators that help to instruct stem cells whether to stay in that state, they play key roles in development.

Young and colleagues have now discovered how microRNAs fit into the map of embryonic stem cell circuitry. With this map, the scientists have moved one step closer to understanding how adult cells can be reprogrammed to an embryonic state and then to other types of cells, and to understanding the role of microRNAs in cancer and other diseases.

"By understanding how master transcription factors turn microRNAs on and off, we now see how these two groups of gene regulators work together to control the state of the cell," says Young, senior author on the study reported in the August 8 issue of Cell. "MicroRNAs are a special class of molecules because they not only contribute to cellular control but they play important roles in disease states such as cancer."

Previous studies had shown that the microRNA machinery is important in maintaining embryonic stem cells in their embryonic state, but offered only partial views of how microRNA genes fit in with the overall gene regulation circuitry. To do so required mapping the sites in the genome from which microRNA genes start, explains Stuart Levine, co-lead author on the paper and postdoctoral scientist i
'/>"/>