The "Roadmap" from Embryonic Stem Cell to Becoming Any Bodily Cell Type. (September 14, 2005)

    While the moral and ethical debates continue to rage regarding the propriety of obtaining and using embryonic stem cells to produce cell types that could be used for therapeutic tissue and organ replacement, biologists have begun, and it is just a beginning, to determine just what happens to cause stem cells to transform into different adult cell types.

It's been known for some time that human ES cells express the genes OCT4, SOX2, and NANOG but exactly what those genes do had remained a mystery although it was suspected that the proteins coded for by them were acting as transcription factors, turning some genes on while keeping others turned off by binding to regions of DNA called promoters.

ScienceNow reports that Richard Young of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and his colleagues find that "the gene trio seems to be a fairly close-knit team, often working together to control other genes. For example, the researchers found evidence that all three proteins camp out just upstream from the DNA that codes for OCT4, presumably keeping the gene turned on. In other cases, the proteins turn off the expression of other well-known genes involved in development of specific tissues."

In fact they "found 623 genes affected by OCT4, 1271 genes that are apparently controlled by SOX2, and 1687 genes controlled by NANOG. A total of 353 genes appear to be controlled by all three."

Clearly these findings a just the beginning of unravelling the extraordinary complexity of the "roadmap" describing the path from ES cells to differentiated adult cells. Stem cell biologist Ari Brivanlou of Rockefeller University in New York points out what ought to be obvious, that detailed molecular knowledge will be crucial before scientists can confidently use ES cell therapies in the clinic or, as Richard Young observes, possibly reversing the process and turning adult cells into the equivalent of ES cells.