How Do Stem Cells Work?

So How Do Stem Cells Work, Anyway?

This is close to the questions researchers at the Whitehead Institute asked in a press release on September 8, 2005. The story was picked up on Science Daily on September 11, 2005. The actual question as framed in the release was, “What exactly makes a stem cell a stem cell?”

The release goes on to say that researchers have found the process by which stem cells are able to become just about any type of cell in the body. This trait (known as pluri-potency) is what makes stem cells interesting and therapeutically useful. But where does it come from?

In the study, researchers focused on three proteins, Oct4, Sox2, and Nanog. These proteins regulate gene expression. According to the release, “These proteins were known to play essential roles in maintaining stem cell identity-if they are disabled, the stem cell immediately begins to differentiate and is thus no longer a stem cell.” The research team used microarray technology[1] to analyze the entire genome of one stem cell. They discovered that the proteins also repress genes which are needed for embryonic growth. When the proteins are inactivated, the new genes “come to life” and the stem cell ceases to be a stem cell and begins to differentiate.

[1] Microarray technology was also used recently in a study which examined the differences between “early” and “late” passage cells in particular lines. See “Stem Cells Mutate in the Lab," 9/16/05, on this blog.

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Science News also picked up on this study and gives more details. According to the Science News Article, "To fill that information gap, the researchers identified the genes to which Oct4, Sox2, and Nanog bind. In the Sept. 23 Cell, the researchers report that these three transcription factors attach to a region of the genome that contains genes that other researchers have shown to control cell development. At least one factor bound to each of 2,260 genes. " Of the 2260 genes, 1303 were active in the stem cells. Some of the active genes made protiens which activated more genes. All 3 of the regulator proteins bind to 353 genes. This suggests that these 3 proteins are "master regulators."

The researchers plan to follow up on their study by "perturbing" the genes and the proteins and seeing how the cells react.