Featured Research

from universities, journals, and other organizations

Stem Cell 'Immortal Strand Hypothesis' Refuted

Date:
August 31, 2007
Source:
University of Michigan
Summary:
How do adult stem cells protect themselves from accumulating genetic mutations that can lead to cancer? For more than three decades, many scientists have argued that the "immortal strand hypothesis" - which states that adult stem cells segregate their DNA in a non-random manner during cell division -- explains it. And several recent reports have presented evidence backing the idea. But new evidence deals a mortal blow to the immortal strand, at least as far as blood-forming stem cells are concerned.

How do adult stem cells protect themselves from accumulating genetic mutations that can lead to cancer?

Related Articles


For more than three decades, many scientists have argued that the "immortal strand hypothesis" - which states that adult stem cells segregate their DNA in a non-random manner during cell division -- explains it. And several recent reports have presented evidence backing the idea.

But in a recent issue of the journal Nature, University of Michigan stem cell researcher Sean Morrison and his colleagues deal a mortal blow to the immortal strand, at least as far as blood-forming stem cells are concerned.

They labeled DNA in blood-forming mouse stem cells and painstakingly tracked its movement through a series of cell divisions. In the end, they found no evidence that the cells use the immortal-strand mechanism to minimize potentially harmful genetic mutations.

"This immortal strand idea has been floating around for a long time without being tested in stem cells that could be definitively identified. This paper demonstrates that it is not a general property of all stem cells," said Morrison, director of the Center for Stem Cell Biology at the U-M Life Sciences Institute.

It remains possible that stem cells in other tissues use this process.

"We've been able to show that this is not a mechanism by which blood-forming stem cells reduce their risk of turning into cancer and, presumably, we should be looking elsewhere to understand what those mechanisms really are," he said.

Stem cells generate all of the tissues in the developing human body, and later in life provide replacement cells when adult tissues are damaged or wear out.

Adult stem cells continue to divide throughout a person's life, replenishing the supply of stem cells while generating other cells that develop into specialized tissues -- muscles, nerves or blood, for example.

Like most cells in the body, adult stem cells divide through mitosis, the process of duplicating the chromosomes and distributing a complete set to each of two daughter cells.

During mitosis, the double-stranded DNA molecule splits into two complementary ribbons of genetic material. Each of the original strands is then used as a template to build two double helixes.

DNA encodes genetic information using a four-letter alphabet. Each time a new strand is assembled alongside the template strand, there's a chance that an incorrect genetic letter will be inserted in the new strand, causing a mutation that could lead to cancer.

The immortal strand hypothesis, proposed in 1975, suggests that dividing adult stem cells always retain the older, or "immortal," template strand. The new, mutation-prone strand goes to daughter cells that give rise to specific tissues.

This non-random distribution process is known as asymmetric chromosome segregation. Adult stem cells use it to minimize their chances of accumulating harmful mutations, according to the immortal strand hypothesis.

To test this idea, Morrison's team administered a DNA-labeling substance called BrdU to mice for several days, giving the DNA time to incorporate the label. Then they extracted the blood-forming stem cells to see how many of them retained BrdU.

If the immortal strand hypothesis is right about asymmetric segregation, then under certain experimental conditions the adult stem cells should hold onto the BrdU label.

"What we found is that not many stem cells retained it," said Morrison, a Howard Hughes Medical Institute researcher.

"In fact, what happened with the label was completely consistent with what you'd expect by random chromosome segregation -- which is known to be how most cells divide -- and was completely inconsistent, in every context we looked, with the immortal strand model."

The experiments also revealed that BrdU is not the general-purpose stem-cell marker many researchers thought it was.

Some scientists have assumed that BrdU-retaining cells found in a variety of tissues are stem cells. But Morrison and his colleagues are the first known to carefully measure stem cell purity among BrdU-retaining cells, and they found it to be "a very insensitive and nonspecific marker."

The Nature paper will be published online Aug 29. The lead author is Mark Kiel of the U-M Life Sciences Institute, the U-M internal medicine department, the U-M Center for Stem Cell Biology, and the Howard Hughes Medical Institute.

"This study suggests that researchers should test BrdU label retention as a marker before assuming it can be used to identify stem cells in other tissues," Kiel said.

In addition to Kiel and Morrison, U-M co-authors are Shenghui He, Rina Ashkenazi, Sara Gentry and Trachette Jackson. Monica Teta and Jake Kushner of the University of Pennsylvania also are also co-authors. The work was supported by the Howard Hughes Medical Institute, the National Institute of Aging, and the U.S. Army Research Laboratory/Office.


Story Source:

The above story is based on materials provided by University of Michigan. Note: Materials may be edited for content and length.


Cite This Page:

University of Michigan. "Stem Cell 'Immortal Strand Hypothesis' Refuted." ScienceDaily. ScienceDaily, 31 August 2007. <www.sciencedaily.com/releases/2007/08/070829143649.htm>.
University of Michigan. (2007, August 31). Stem Cell 'Immortal Strand Hypothesis' Refuted. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2007/08/070829143649.htm
University of Michigan. "Stem Cell 'Immortal Strand Hypothesis' Refuted." ScienceDaily. www.sciencedaily.com/releases/2007/08/070829143649.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins