Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Scientists Discern Signatures of Old Versus Young Stem Cells

Published: Wednesday, July 03, 2013
Last Updated: Wednesday, July 03, 2013
Bookmark and Share
A chemical code scrawled on histones determines which genes in that cell are turned on and which are turned off.

Now, Stanford University School of Medicine researchers have taken a new step in the deciphering of that histone code.

In a study published June 27 in Cell Reports, a team led by Thomas Rando, MD, PhD, professor of neurology and neurological sciences and chief of the Veterans Affairs Palo Alto Health Care System’s neurology service, has identified characteristic differences in “histone signatures” between stem cells from the muscles of young mice and old mice. The team also distinguished histone-signature differences between quiescent and active stem cells in the muscles of young mice.

“We’ve been trying to understand both how the different states a cell finds itself in can be defined by the markings on the histones surrounding its DNA, and to find an objective way to define the ‘age’ of a cell,” said Rando, who is also director of Stanford’s Glenn Laboratories for the Biology of Aging and deputy director of the Stanford Center on Longevity.

While all cells in a person’s body share virtually the same genes, these cells can be as different from one another as a nerve cell is from a fat cell. This is because only a fraction of a cell’s genes are actually “turned on” — actively involved in the production of one or another protein. A muscle cell produces the proteins it uses to be a muscle cell, a liver cell produces those it needs in order to be a liver cell and so forth. Rando’s team thinks the same kinds of on/off differences may distinguish old stem cells from young stem cells.

In human cells, the DNA in which genes are found doesn’t float loose inside the cell nucleus but is, rather, packaged inside protein “husks” called histones. Chemical marks on the histones, which sheathe our chromosomal DNA in each cell’s nucleus, act as “stop” and “go” traffic signals. These signals tell the complex molecular machinery that translates genes’ instructions into newly produced proteins which genes to read and which ones to skip.

In 2005, Rando and his colleagues published a study in Nature showing that stem cells in several tissues of older mice, including muscle, seemed to act younger after continued exposure to younger mice’s blood. Their capacity to divide, differentiate and repopulate tissues, which typically declines with an organism’s advancing age, resembled those of their stem-cell counterparts in younger animals.

This naturally led to curiosity about exactly what is happening inside a cell to rejuvenate it, said Rando. One likely place to look for an answer was histones, to see if changes in the patterns of the chemical marks on them might reveal any secrets, at the cellular level, of the aging process we all experience — and, perhaps, whether there might be anything we can do about it. Rando and his colleagues also wanted to learn more about what kinds of difference in these patterns accompany a cell’s transition from one level of activity to another.

To do that, Rando and his team looked at satellite cells, an important class of stem cells that serve as a reserve army of potential new muscle tissue. Under normal circumstances, these rather rare stem cells sit quietly adjacent to muscle fibers. But some signal provided by muscular injury or degeneration prompts satellite cells to start dividing and then to integrate themselves into damaged fibers, repairing the muscle tissue. The investigators profiled the histone markings of mice that are as old, in mouse years, as young human adults, as well as mice whose human counterparts would be 70 to 80 years old.

The researchers harvested satellite cells from both healthy and injured muscle tissue of young mice and from healthy tissue of old mice; extracted these cells’ DNA with the histone coatings intact; and used tagged antibodies targeting the different kinds of marks to find which spots on those histones were flagged with either “stop” or “go” signals.

“Satellite cells can sit around for practically a lifetime in a quiescent state, not doing much of anything. But they’re ready to transform to an activated state as soon as they get word that the tissue needs repair,” Rando said. “So, you might think that satellite cells would be already programmed in a way that commits them solely to the ‘mature muscle cell’ state.” The researchers expected that in these quiescent stem cells, the genes specific for other tissues like skin and brain would be marked by “stop” signals.

Instead, they found, in quiescent satellite cells taken from the younger mice, copious instances in which histones in the vicinity of genes ordinarily reserved for other tissues were marked with both “stop” and “go” signals, just as genes associated with development to mature-muscle status were.

“We weren’t looking for that, and we certainly weren’t expecting it,” Rando said. “We figured all the muscle genes would be either poised for activity — marked with both ‘on’ and ‘off’ signals — or ‘on,’ and that all the other genes would be turned off. But when you look at these satellite cells the way we did, they seem ready to become all kinds of cells. It’s a mystery,” he said, suggesting that it could mean stem cells thought to be committed to a particular lineage may be capable of becoming other types of tissue entirely.

“Maybe their fates are not permanently sealed,” he said. “The door is not locked. Who knows what could happen if they’re given the right signals?” The Rando lab is now beginning to test this proposition.

Oddly, activated satellite cells from injured muscle tissue featured far more gene-associated “stop” signals than did quiescent ones. “As a cell goes from quiescent to activated state, you might expect to see more genes marked by ‘on’ signals,” Rando said. “We found the opposite. The dominant pattern when cells become activated is a big increase in repressive marks across the genome. Apparently it’s not until then that a satellite cell makes the effort to turn off all of its non-muscle options.”

The differences between quiescent and activated cells, Rando’s team found, are mirrored by those between young and old quiescent satellite cells. “With age, there’s an uptick in repressive markers. A lot more genes are locked in the ‘off’ position,” he said.

The meaning of this is not yet clear, he added. “In a division-capable cell, as opposed to the nondividing, differentiated muscle cells that activated satellite cells may someday become, it may be important to maintain a high level of repression with age. Maybe this increase in repression is a kind of tumor-suppression mechanism, keeping aging satellite cells — which could have accumulated some dangerous mutations over the passing months and years — in check.”

The description of the histone-code differences between young and old cells constitutes a yardstick allowing investigators to ask which of these differences are important in aging and in rejuvenation, Rando said.

“We don’t have the answers yet. But now that we know what kinds of changes occur as these cells age, we can ask which of these changes reverse themselves when an old cell goes back to becoming a young cell” — as appeared to be the case when tissues of older mice were exposed to blood from younger mice.

Rando’s group is now looking to test whether the signatures they’ve identified in satellite cells generalize to other kinds of adult stem cells as well.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More Than 4,400+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

$10M Grant Funds Infection-Focused Center
The new center will explore intracellular and intercellular processes by which salmonella bacteria, responsible for more than 100 million symptomatic infections annually, infect immune cells.
Wednesday, April 06, 2016
Resurrecting an Abandoned Drug
Previously discarded drug shows promise in helping human cells in a lab dish fight off two different viruses.
Wednesday, March 30, 2016
Fracking's Impact on Drinking Water Sources
A case study of a small Wyoming town reveals that practices common in the fracking industry may have widespread impacts on drinking water resources.
Wednesday, March 30, 2016
Imaging Cells and Tissues Under the Skin
First technique developed for viewing cells and tissues in three dimensions under the skin.
Tuesday, March 22, 2016
Glucose-Guzzling Immune Cells May Drive Coronary Artery Disease
Researchers at Stanford University have found excessive glucose uptake by inflammatory immune cells called macrophages, which reside in arterial plaques, may be behind coronary artery disease.
Wednesday, March 16, 2016
Ultra-Sensitive Test for Cancers, HIV
Test developed that is thousands of times more sensitive than current diagnostics.
Tuesday, March 15, 2016
Weighing up the Risk of Groundwater Contamination
Faulty, shallow wells can leak oil and natural gas into underground drinking-water supplies, Stanford Professor Rob Jackson finds.
Wednesday, February 24, 2016
Blood Test Could Transform TB Diagnosis
A simple blood test that can accurately diagnose active tuberculosis could make it easier and cheaper to control a disease that kills 1.5 million people every year.
Tuesday, February 23, 2016
Paper Published Based on RNA Game
Video-gamers have co-authored a paper describing a new set of rules for determining the difficulty of designing structures composed of RNA molecules.
Thursday, February 18, 2016
Marker Identifies Most Basic Form of Blood Stem Cell
Nearly 30 years after the discovery of the hematopoietic stem cell, Stanford researchers have found a marker that allows them to study the version of these stem cells that continues to replicate.
Wednesday, February 17, 2016
Flexible Gene Expression May Regulate Social Status
Scientists show how the selective expression of genes through epigenetics can regulate the social status of African cichlid fish.
Monday, January 11, 2016
World Forest Carbon Stocks Overestimated
Researchers with The Natural Capital Project show how fragmentation harms forests' ability to store carbon; more restoration is needed to reconnect forest patches.
Tuesday, January 05, 2016
U.S. Needs a New Approach for Governance of Risky Research
The United States needs better oversight of risky biological research to reduce the likelihood of a bioengineered super virus escaping from the lab or being deliberately unleashed, according three Stanford scholars.
Monday, January 04, 2016
Mapping the Mechanical Properties of Living Cells
Researchers have developed a new way to use atomic force microscopy to rapidly measure the mechanical properties of cells at the nanometer scale, an advance that could pave the way for better understanding immune disorders and cancer.
Monday, December 21, 2015
Viral Infections Leave a Signature on the Immune System
A test that queries the body’s own cells can distinguish a viral infection from a bacterial infection and could help doctors know when to use antibiotics.
Thursday, December 17, 2015
Scientific News
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Apricot Kernels Pose Risk of Cyanide Poisoning
Eating more than three small raw apricot kernels, or less than half of one large kernel, in a serving can exceed safe levels. Toddlers consuming even one small apricot kernel risk being over the safe level.
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Understanding Female HIV Transmission
Glowing virus maps points of entry through entire female reproductive tract for first time.
Genetic Markers Influence Addiction
Differences in vulnerability to cocaine addiction and relapse linked to both inherited traits and epigenetics, U-M researchers find.
Lab-on-a-Chip for Detecting Glucose
By integrating microfluidic chips with fiber optic biosensors, researchers in China are creating ultrasensitive lab-on-a-chip devices to detect glucose levels.
A lncRNA Regulates Repair of DNA Breaks in Breast Cancer Cells
Findings give "new insight" into biology of tough-to-treat breast cancer.
COPD Linked to Increased Bacterial Invasion
Persistent inflammation in COPD may result from a defect in the immune system that allows airway bacteria to invade deeper into the lung.
Detection of HPV in First-Void Urine
Similar sensitivity of HPV test on first void urine sample compared to cervical smear.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!