New technique produces genetically identical stem cells

July 1, 2008

Adult cells of mice created from genetically reprogrammed cells—so-called induced pluripotent stem (IPS) stem cells—can 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, because all cells in the mouse contain the same number of viral integrations in the same location within the genome. With previous approaches, each reprogrammed cell differed because the viruses used to insert the reprogramming genes could integrate anywhere in the cell's DNA with varying frequency.

Wernig and Lengner's method also increases the reprogramming efficiency from one in a thousand cells to one in twenty.

The large numbers of IPS cells that can be created by this method can aid experiments requiring millions of identical cells for reprogramming, such as large-scale chemical library screening assays.

"In experiments, the technique will eliminate many of the reprogramming process's unpredictable variables and simplify enormously the research on the reprogramming mechanism and the screening for virus replacements," says Jaenisch, who is also a professor of biology at Massachusetts Institute of Technology.

Source: Whitehead Institute for Biomedical Research

Explore further: Research papers shed light on decade-long stem cell mystery

Related Stories

OSKM stoichiometry determines iPS cell reprogramming

March 13, 2015

Researchers at Kyoto University's Center for iPS Cell Research and Application discover a simple way to increase the production of induced pluripotent stem cells. A major hurdle in reprogramming science is generating a sufficient ...

One step closer to cell reprogramming

May 6, 2014

In 2012, John B. Gurdon and Shinya Yamakana were awarded the Nobel Prize in medicine for discovering that adult cells can be reprogrammed into pluripotent ones (iPS); the cells obtained are capable of behaving in a similar ...

Recommended for you

A not-quite-random walk demystifies the algorithm

December 15, 2017

The algorithm is having a cultural moment. Originally a math and computer science term, algorithms are now used to account for everything from military drone strikes and financial market forecasts to Google search results.

Heavy oils and petroleum coke raising vanadium emissions

December 15, 2017

Human emissions of the potentially harmful trace metal vanadium into Earth's atmosphere have spiked sharply since the start of the 21st century due in large part to industry's growing use of heavy oils, tar sands, bitumen ...

Single-photon detector can count to four

December 15, 2017

Engineers have shown that a widely used method of detecting single photons can also count the presence of at least four photons at a time. The researchers say this discovery will unlock new capabilities in physics labs working ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.