Extreme makeover: Scientists explore new way to change cell's identity

May 05, 2009

Even cells aren't immune to peer pressure. Scientists at the Stanford University School of Medicine have now shown that skin cells can be coaxed to behave like muscle cells -- and muscle cells like skin cells -- solely by altering who they hang out with: the relative levels of the ingredients inside the cell.

The fickleness of the cells, and the relative ease with which they make the switch, provide a glimpse into the genetic reprogramming that must occur for a cell to become something it's not.

"We'd all like to understand what happens inside the black box," said Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor and member of Stanford's Stem Cell Biology and Institute. "These types of experiments will help us to identify the earliest regulators of reprogramming."

Harnessing these genetic makeovers will allow scientists to better understand how to induce specialized to revert to a stem-cell-like state in a process called induced pluripotency. These newly pluripotent, or iPS, cells, which can then be encouraged to branch out into a variety of other cell types, have shown increasing promise as possible therapies for disorders like diabetes. But Blau's experiments suggest an intriguing alternative to iPS: that of enticing specialized adult cells to move sideways from one developmental fate to another without requiring a dip into the stem cell pool.

Blau, who directs the Baxter Laboratory of Genetic Pharmacology at the medical school, is the senior author of the research, which is published in the May issue of the . She and her laboratory members fused mouse muscle cells with human to create hybrids called heterokaryons. In heterokaryons, the nuclei of each cell type remains distinct, and the influence of one on the nature of the other can be clearly distinguished. They then examined the hybrids to see if they began to look and act more like muscle cells, skin cells or something in between.

The researchers use species-specific differences to track the unique gene-expression profiles of each cell type. They found that if the muscle outnumbered the skin cell nuclei, the skin nuclei began to express muscle-specific genes within a few hours of fusion. When the skin cell nuclei were more numerous, the muscle cell nuclei switched to express skin-specific genes. What's more, the heterokaryons themselves assumed the morphology of the ruling cell type — flat and roundish like skin cells or long and skinny like muscle cells.

"We were especially pleased to see that the muscle cells could begin to act like skin," said Blau, whose laboratory had previously shown in similar experiments that can influence the fate of other cells. "But now we know it can go both ways."

The outnumbered nuclei assumed their new identities both quickly and decisively — there was a telling lack of cells expressing characteristics of both muscle and skin.

"It's all or nothing," said Blau. "At a certain threshold, a switch is flipped and the cell becomes committed to a specific fate." Although the precise molecular regulators of such a switch have not yet been identified, Blau speculates that proteins or small RNAs in the cytoplasm of the predominant cell modify the gene expression program of the minority nuclei.

In addition to homing in on these regulators, the researchers are repeating the experiment with a variety of different cell types. "This shows that it can be done," said Blau. "Currently, inducing pluripotency in adult is time consuming and inefficient. We'd like to improve on that, or explore ways to skip that step altogether. We're coming at the problem from all angles."

Source: Stanford University Medical Center (news : web)

Explore further: Life's extremists may be an untapped source of antibacterial drugs

add to favorites email to friend print save as pdf

Related Stories

Inflammation triggers cell fusions that could protect neurons

Apr 20, 2008

Chronic inflammation triggers bone marrow-derived blood cells to travel to the brain and fuse with a certain type of neuron up to 100 times more frequently than previously believed, according to a new study from the Stanford ...

Muscle stem cell identity confirmed by Stanford researchers

Sep 17, 2008

A single cell can repopulate damaged skeletal muscle in mice, say scientists at the Stanford University School of Medicine, who devised a way to track the cell's fate in living animals. The research is the first to confirm ...

New technique produces genetically identical stem cells

Jul 01, 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 ...

Recommended for you

Cohesin molecule safeguards cell division

22 hours ago

The cohesin molecule ensures the proper distribution of DNA during cell division. Scientists at the Research Institute of Molecular Pathology (IMP) in Vienna can now prove the concept of its carabiner-like ...

Nail stem cells prove more versatile than press ons

23 hours ago

There are plenty of body parts that don't grow back when you lose them. Nails are an exception, and a new study published in the Proceedings of the National Academy of Sciences (PNAS) reveals some of the r ...

Scientists develop 3-D model of regulator protein bax

Nov 21, 2014

Scientists at Freie Universität Berlin, the University of Tubingen, and the Swiss Federal Institute of Technology in Zurich (ETH) provide a new 3D model of the protein Bax, a key regulator of cell death. When active, Bax ...

Researchers unwind the mysteries of the cellular clock

Nov 20, 2014

Human existence is basically circadian. Most of us wake in the morning, sleep in the evening, and eat in between. Body temperature, metabolism, and hormone levels all fluctuate throughout the day, and it ...

User comments : 0

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.