The 'holy grail' of stem cells is pursued

CorrespondentSeptember 27, 2010 

— Stem cells mature into most types of cells in the body, but what makes a stem cell a stem cell? Until now, scientists didn't know.

Using mouse embryonic stem cells, Yi Zhang, a UNC-Chapel Hill biochemistry and biophysics professor and Howard Hughes Medical Institute investigator, identified a protein called Tet 1 as being the "on" switch for a stem cell.

Tet 1 activates a gene called Nanog that helps stem cells reproduce and maintain their pluripotency - the ability to become any type of cell.

According to Zhang, understanding how Tet 1 and Nanog interconnect could lay the groundwork for eventually turning one type of cell in the body into another.

"Tet 1 could potentially direct mature cells to regress and differentiate into a different type of cell," he said. "It is possible that Tet 1 could be used to push skin or other types of cells back into stem cells."

It would be theoretically possible, Zhang said, to manipulate these reprogrammed cells to mature into the cells patients need to fight disease, such as insulin cells in a person with diabetes.

To test how Tet 1 functions in nature, Zhang's team turned the protein off in one cell of a two-celled mouse embryo. The cells that contained active Tet 1 continued to grow into stem cells. Cells without Tet 1 become trophoblast cells - cells that largely develop into the placenta and nourish the growing embryo.

Finding the root of what gives a stem cell its ability to morph into other cell types is cause for excitement, said Dr. Nelson Chao, stem cell expert and chief of the cellular therapy division at Duke University Medical Center. But he cautioned that identifying Tet 1 will not cure major diseases just yet.

"This is the holy grail in stem cell biology," Chao said. "But understanding the basics of how 'stemness' works and translating it to clinical interventions are different things entirely."

Before using reprogrammed cells, he said, investigators must determine whether their life span mirrors that of natural stem cells and whether they become malignant in time.

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