How do stem cells in the adult protect themselves from accumulating genetic mutations that can cause cancer?
Mark Kyle
In the last three decades, many scientists supported the immortal strand hypothesis, which states that adult stem cells separate their DNA in a non-arbitrary way during cell division and claimed that it protects the stem cell from accumulating mutations. Also, several studies have recently been published that present findings that confirm this claim.
But in one of the latest issues of the magazine "Nature", the stem cell researcher from the University of Michigan Sean Morrison and his research partners landed from death to the immortal strand, at least when it comes to stem cells that produce blood cells.
They labeled DNA in blood cell-forming stem cells in a mouse and followed its movements meticulously during a series of cell divisions. Ultimately, they found no evidence that stem cells use the immortal strand mechanism to minimize potentially dangerous genetic mutations.
"The idea of this immortal strand has been circulating for a long time without being tested in stem cells that can be identified with certainty. This paper shows that this property does not characterize all stem cells," said Morrison, head of the Center for Stem Cell Biology at the University of Michigan Life Sciences Institute.
It is still possible that stem cells in other tissues use this mechanism.
"We were able to show that this is not the mechanism that cell-forming stem cells also use to reduce the risk of becoming cancerous, and we probably need to look in another way for what these mechanisms are," said Morrison.
Stem cells form all the tissues in the developing human body, and later in life provide replacement cells when mature tissues are damaged or worn away.
Adult stem cells continue to divide throughout a person's life, thereby refreshing the pool of stem cells themselves as well as creating other cells that differentiate into specialized tissues such as muscle, nerve or blood.
Like most cells in the body, stem cells divide by mitosis, the process of doubling the chromosomes and distributing a complete set to each of the two daughter cells.
During mitosis, the double-stranded DNA molecule separates into two complementary strands of genetic material. Each such strand forms a template for creating two double coils.
DNA encodes information using four letters. Every time a new strand is built along the old strand there is a chance that an incorrect genetic signal will be inserted into the new strand, which will create a mutation that can cause cancer.
The immortal strand hypothesis, proposed in 1975, holds that the dividing stem cell in an adult always leaves the old or 'immortal' template strand. The new, mutation-prone strand is transferred to the daughter cells that form specific tissues.
This process of non-random division is called asymmetric chromosome segregation. Adult stem cells use it to reduce the chance of accumulating dangerous mutations, according to the immortal strand hypothesis.
To test this idea, Morrison's research group gave mice a DNA marker, called BrdU, for several days, in order to give the DNA time to absorb the marker. They then extracted the blood cell-forming stem cells and tested how many of them retained the BrdU.
If the immortal strand hypothesis is correct regarding asymmetric segregation, under certain experimental conditions the stem cell will retain the BrdU marker.
"What we found is that many of the stem cells did not retain the marking," said Morrison, a researcher at the Howard Hughes Medical Center.
"In fact, what happened with the marking is completely consistent with what we would expect to happen in random segregation of the chromosomes - which is known as the way in which most cells divide - and was completely inconsistent, in every context we examined, with the immortal strand hypothesis."
The experiments also showed that BrdU is not a versatile marker for stem cells as many researchers believed.
A number of researchers assumed that cells that retain BrdU found in various tissues are stem cells. But Morrison and his collaborators are the first known to have carefully tested the 'purity' of the stem cells between the cells containing BrdU, and they found that this is a "very insensitive and non-specific marker".
The article in the journal Nature was published online on August 29. The lead author is Mark Kyle of the University of Michigan Life Sciences Institute, the University of Michigan Department of Internal Medicine, and the Howard Hughes Medical Institute.
"This study argues that researchers should examine the retention of BrdU in cells as a marker before assuming that this method can be used to identify stem cells in other tissues," says Kyle.
Apart from Kyle and Morrison, other researchers from the University of Michigan participating in the study are Shangwei Ha, Rina Ashkenazi, Sarah Gentry and Tresht Jackson. Monica Theta and Jake Kushner of the University of Pennsylvania also co-authored the paper. The work was supported by the Howard Hughes Medical Institute, the National Institute on Aging and the US Army Research Laboratory.
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Thanks Roy.
There are stem cells in the muscle area. These stem cells are very limited - they can differentiate almost exclusively into muscle cells, and they do that too with excruciating slowness. They are the reason why muscles have the ability to recover (albeit slowly and ineffectively in serious injuries) from injury.
Other stem cells exist in the bone marrow and replenish the pool of red blood cells (which carry oxygen in the blood) and white blood cells, which protect the body. They are called 'mesenchymal stem cells'.
Perhaps the largest reservoir of stem cells in the body is under the skin. Every day we sing more than 50 million cells. Stem cells found in the lower layer of the skin take care of constantly dividing and producing new skin cells to compensate for the ones we lose.
New studies also claim that stem cells can be found in the heart muscle and brain, but it is still not clear how true this is, or what the full capacity of these cells is.
There are stem cells in adults as well, mainly in the bone marrow, but their range of variation is between different types of blood cells, and not every cell in the body like fetal stem cells.
Is it just me who doesn't understand??
Where did stem cells suddenly appear in the body of an adult?
After all, we were told all the time about the attempts to preserve the umbilical cord, which is the only place where stem cells remained, as well as in embryos...and now it turns out that there are stem cells in any amount in all body tissues, and not only that, but what is written in the biology books, which explains that the muscle cells do not regenerate, is not accurate and that these cells regenerated by stem cells!!
I have to admit that the more I follow the stem cells, the surprises never end. By the way, does the division of the normal cells still exist? Or has it already passed!?