Dalton's new work addressed the uncertainty about how Myc maintains the pluripotency of stem cells by examining what happens when two forms of Myc-c-Myc and N-Myc-are inactivated in pluripotent stem cells. What he found was that either c- or N-Myc is sufficient to maintain pluripotency, but that the absence of both triggers the differentiation of pluripotent stem cells. Myc is therefore acting as a "brake" to restrain differentiation. When the "differentiation brake" is removed, cells lose their stem cell properties, and, potentially, they can become any one of over a hundred different cell types.

Pluripotent stem cells can now be made from skin fibroblasts and even from blood samples. (Fibroblasts are cells common in connective tissues of animals and play an important role in the healing of wounds, among many functions.) The conversion of mature fibroblast or blood cells back to pluripotent stem cells is called "reprogramming." Myc also has a critical role in this process. The ability to make stem cells from a patient's blood or skin is going to revolutionize medicine as it opens the way for patient-specific stem cells that would circumvent problems associated with immune rejection, said Dalton.

"During the reprogramming of cells, Myc represses genes associated with the differentiated state and primes them for the expression of stem cell genes," he said. "We now speculate that during the early reprogramming stage, Myc serves to change the cell cycle so that stem cells can divide for long periods of time without aging. This is also what Myc does in cancer cells."

Dalton said that there is an intriguing relationship between normal stem cells and cancer cells. Since Myc is crucial for maintenance of stem cells and for the development of cancer, pluripotent stem cells represent a good model for tumor biologists. Cancer is thought to be initiated by rogue stem cells found in different tissues, further highlighting the link between stem cell biology, cancer and Myc.

"This is clearly going to be a major area of research for many years to come," Dalton said.

Source: University of Georgia