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Issue date: 2/28/08
Science

MIT researchers convert skin cells to stem cells

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In this month's issue of Cell Stem Cell, scientists at MIT's Whitehead Institute for Biomedical Research continue their groundbreaking work on pluripotent stem cells. The team headed by Rudolf Jaenisch shows that a specific sequence of biochemical manipulations can reprogram a skin cell into a pluripotent stem cell.

In 2006, research led by Shinya Yamanaka at Kyoto University, Japan, showed that skin cells from mice could be reprogrammed, or reverted, to a pluripotent stem cell (termed iPS, for induced pluripotent stem cell) using four key pluripotent-associated genes. Pluripotency is the condition in which a cell can become any cell type in the body, such as muscle, skin or neurons.

The cells derived from pluripotent cells are said to be differentiated. These cells are unable to become other cells in the body because the structure of their nuclei is restrictive and certain genes are turned off.

Yamanaka's work was the first to show that differentiated cells could become pluripotent cells, a feat once thought to be impossible. It opened a new door in the search to create patient-specific stem cells, which can be used for medical treatments.

However, as promising as this initial work was, there were problems. The reprogrammed cells were not fully pluripotent. Also, the four reprogramming genes were introduced into the cell using a virus. Furthermore, one of the four genes is known to be oncogenic, or cancer-causing.

Three groups headed by Yamanaka, Jaenisch and a team from UCLA remedied the first problem in the summer of 2007. They showed that these new iPS cells were fully pluripotent, having characteristics of true pluripotent stem cells.

Finally, in November 2007, Yamanaka, as well as a team from Wisconsin, reprogrammed human skin cells, taking the research one step closer to clinical applications.

Until now the research in this area has been poorly understood at the molecular level. Is reactivation of pluripotency a random process or does it require a specific sequence of molecular events? Furthermore, do the four genes required to start the process of reprogramming interfere with differentiation later on? Jaenisch and his team answered these questions.
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