New technique produces genetically identical ...( CAMBRIDGE Mass. (July 1 2008) Adul...)

CAMBRIDGE, Mass. (July 1, 2008) Adult cells of mice created from genetically reprogrammed cellsso-called induced pluripotent stem (IPS) stem cellscan be triggered via drug to enter an embryonic-stem-cell-like state, without the need for further genetic alteration.

The discovery, which promises to bring new efficiencies to embryonic stem cell research, is reported in the July 1, 2008, online issue of Nature Biotechnology.

"This technical advancement will allow thousands of identical reprogrammed cells to be used in experiments," says Marius Wernig, one of the paper's two lead authors and a postdoctoral researcher in Whitehead Member Rudolf Jaenisch's lab.

"Using these cells could help define the milestones of how cells are reprogrammed and screen for drug-like molecules that replace the potentially cancer-causing viruses used for reprogramming," adds Christopher Lengner, the other lead author and also a postdoctoral researcher in the Jaenisch's lab.

In the current work, Wernig and Lengner made mice created in part from the embryonic-stem-cell-like cells known as IPS cells. The IPS cells were created by reprogramming adult skin cells using lentiviruses to randomly insert four genes (Oct4, Sox2, c-Myc and Klf4) into the cells' DNA. The IPS cells also were modified to switch on these four genes when a drug trigger, doxycycline, is added to the cells.

Wernig and Lengner then took cells from each IPS mouse and introduced the doxycycline trigger, thereby changing the adult mouse cells into IPS cells.

While earlier reprogramming experiments have typically induced pluripotency in adult skin cells, Wernig and Lengner were able to employ this novel method to successfully reprogram multiple cell and tissue types, including cells of the intestine, brain, muscle, kidney, adrenal gland, and bone marrow. Importantly, the technique allows researchers to create large numbers of genetically identical IPS cells, bec
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