Researcher discovers mechanism for changing adult cells into stem-like cells

October 7, 2010

In 2006, Dr. Shimya Yaminaka of Kyoto University in Japan set the stem cell and regenerative medicine research world on fire when he successfully transformed differentiated mouse skin cells into cells that looked and behave like embryonic stem cells. Embryonic stem cells, the subject of much controversy when used in research, have the ability to differentiate into any type of tissue.

Yaminaka's creation of induced pluripotent [iPSCs] meant that in the future, research to improve human disease might be able to use iPSCs in lieu of . Since then, researchers around the world have been able to replicate his process. However, no one has been able to unlock the mechanism that allows cells to be regressed from differentiated to undifferentiated cells—until now.

University of Colorado Cancer Center researcher Chuan-Yuan Li, PhD, and his group have discovered that so-called "grim-reaper" caspase genes are the gatekeepers that can open the door to allow differentiated adult cells to regress to undifferentiated iPSCs.

"By doing experiments in which we added caspase inhibitor genes to the Yaminaka protocol, we discovered that when caspases are turned off, you cannot make IPSCs," says Li, professor of radiation oncology at the University of Colorado School of Medicine. "We were able to shut down the process almost completely."

The discovery is the cover article in the Oct. 8, 2010 issue of Cell Stem Cell.

"For practical reasons, the discovery is important because even though the transformation to iPSCs is a straightforward process on surface, it is not very efficient, and this information can help increase efficiency," Li says. "It can also help with the problem of cells that don't complete the transformation process acting like cancer cells. And from a purely scientific perspective, it is fascinating to understand why the magic happens."

Li's group had been working on the roles of caspases in wound healing when Yaminaka published his initial iPSC work in mice. That got Li thinking about potential roles of caspases in iPSC generation.

"I thought maybe caspases could also induce iPS cells instead of the four transcriptional factors that Yamanaka used," he says. "If that was true, it would be very exciting."

For six months, his group tried different experiments using various caspase genes to coax human skin cells into iPS cells, but they had no success. Although caspases were not sufficient to make iPS cells, Li kept going with the idea that caspases were somehow involved.

They made their discovery when they introduced the caspase inhibitors into , which almost completely shut down the induction of iPS cells.

Caspases, Li says, appear to loosen up the built-in controls that make a cell differentiated or undifferentiated, just like a clutch allows a driver to switch gears while driving. Undifferentiated stem-like cells and differentiated cells from one person have the exact same genes. The difference between them is which genes are turned on or off.

In other words, he says, caspases could be the key to a kind of cellular reincarnation—taking a cell that, during human development, became a skin cell back to its original state to become any kind of cell.

"About twenty years ago, a scientist who was among the first to clone the caspase 3 gene named the gene Yama, the Hindu Lord of Death who was responsible for both killing a being and setting him on his way into his reincarnated life," Li said. "It is now becoming clear that caspases don't just kill, but they can change the cell's fate. They could be a mediator of epigenetic changes in multi-cellular organisms."

Explore further: Study: Skin cells turned into stem cells

Related Stories

Study: Skin cells turned into stem cells

August 22, 2005

The controversy over embryonic stem cell research may become moot with a procedure that turns skin cells into what appear to be embryonic stem cells.

How Useful Are Adult Stem Cells, Really?

April 26, 2010

(PhysOrg.com) -- With the debate (especially in the U.S.) raging over ethics of using embryonic stem cells in research to cure diseases like ALS, Parkinsons, Type 1 diabetes and even spinal cord injuries, the breakthrough ...

New type of human stem cell may be more easy to manipulate

June 8, 2010

Researchers from the Massachusetts General Hospital Center for Regenerative Medicine (MGH-CRM) and the Harvard Stem Cell Institute have a developed a new type of human pluripotent stem cell that can be manipulated more readily ...

Recommended for you

Genomes uncover life's early history

August 24, 2015

A University of Manchester scientist is part of a team which has carried out one of the biggest ever analyses of genomes on life of all forms.

Rare nautilus sighted for the first time in three decades

August 25, 2015

In early August, biologist Peter Ward returned from the South Pacific with news that he encountered an old friend, one he hadn't seen in over three decades. The University of Washington professor had seen what he considers ...

Study shows female frogs susceptible to 'decoy effect'

August 28, 2015

(Phys.org)—A pair of researchers has found that female túngaras, frogs that live in parts of Mexico and Central and South America, appear to be susceptible to the "decoy effect." In their paper published in the journal ...

Why a mutant rice called Big Grain1 yields such big grains

August 24, 2015

(Phys.org)—Rice is one of the most important staple crops grown by humans—very possibly the most important in history. With 4.3 billion inhabitants, Asia is home to 60 percent of the world's population, so it's unsurprising ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Nevertheless
not rated yet Oct 08, 2010
And you heard it here first! REAL rejuvenation therapy started with this discovery. Now the race is on!

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.