July 15, 2024

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Science Advances: Is the bigger the stem cell the better?

Science Advances: Is the bigger the stem cell the better?


Science Advances: Is the bigger the stem cell the better?



Adult stem cells are vital to the maintenance of many tissues in our body. For example, hematopoietic stem cells build the blood system throughout life.

tem cells are very small. Recent studies have found that mouse and artificial hematopoietic stem cells expand during aging.

The size of small cells is important for the function of stem cells in the body, and it is proposed that the expansion of stem cells will reduce their function during aging.

Biologists at the Massachusetts Institute of Technology answered an important biological question: Why do cells control their size?


Cells of the same type are surprisingly consistent in size, while cells of different types have different sizes. This raises the question: Is cell size important for cell physiology?


Researchers have discovered that hematopoietic stem cells are one of the smallest cells in the body. As they grow larger, they lose the ability to perform normal functions—replenishing blood cells in the body. However, when the cells return to their normal size, they behave normally again.


Researchers also found that with age, hematopoietic stem cells tend to expand. Their research shows that this increase leads to a decrease in stem cells during aging.


Jette Lengefeld, former postdoctoral fellow at the Massachusetts Institute of Technology and now principal researcher at the University of Helsinki, said: “We have found that cell enlargement is a new aging factor in the body. Now we can explore whether we can treat cell enlargement to delay aging and be related to aging. Disease.”


Lengefeld is the lead author of the study, which was titled “Cell size is a determinant of stem cell potential during aging” published in the November 12th issue of “Science Advances”. The late Angelika Amon, a professor of biology at MIT and a member of the Koch Cancer Institute, was the senior author of the study.


Science Advances: Is the bigger the stem cell the better?




Big influence


Since the 1960s, it has been known that human cells grown in laboratory petri dishes increase with aging (a state of non-dividing cells related to aging). Every time a cell divides, it encounters DNA damage. When this happens, the “split” will stop to repair the damage.

During each delay, the cells will grow slightly larger. Many scientists believe that this increase is just a side effect of aging, but Amon’s laboratory began to study the possibility of large cell size causing loss of aging-related functions.


Lengefeld studied the effect of size on stem cells, especially hematopoietic stem cells, which produce blood cells throughout our body.

To study how size affects these stem cells, researchers damaged their DNA, causing them to grow. Then, they compared these enlarged cells with other cells that also experienced DNA damage but were prevented from growing with the drug rapamycin.


After the treatment, the researchers injected the two groups of stem cells into mice whose blood stem cells had been eliminated to measure their functions. This allowed the researchers to determine whether the transplanted stem cells could repopulate the blood cells of the mice.


They found that stem cells with damaged and enlarged DNA were unable to produce new blood cells. However, stem cells with damaged DNA can still produce new blood cells.


In another experiment, the researchers used a genetic mutation to reduce the size of naturally occurring large stem cells that they found in old mice. They showed that if they induce these large stem cells to become smaller again, these cells will regain their regenerative potential and behave like young stem cells.


Lengefeld said: “This is an amazing proof that the size of stem cells is very important to their function. When we destroy the DNA of stem cells but keep them small during the destruction process, they retain their function. If we shrink The volume of large stem cells can restore their functions.”



Keep cells “small”


When the researchers started treating mice with rapamycin when they were very young, they were able to prevent the growth of hematopoietic stem cells as the mice got older. The hematopoietic stem cells extracted from these mice are still small, and young stem cells can be generated even in 3-year-old mice-which is very old for mice.


Rapamycin is a drug that can inhibit cell growth. It is now used to treat some cancers and prevent organ transplant rejection. It has attracted interest because of its ability to extend the lifespan of mice and other organisms. Lengefeld said it may help slow the expansion of stem cells, so it may be beneficial to humans.


She said: “If we find drugs that can make large hematopoietic stem cells smaller, we can test whether it can improve the health of people with blood system problems, such as anemia and lowered immune systems, and may even help leukemia patients.”


The researchers also proved the importance of another type of stem cell-the size of intestinal stem cells. They found that larger stem cells have a weaker ability to produce intestinal organoids that mimic the structure of the intestinal lining.


Lengefeld said: “This shows that the relationship between cell size and function in stem cells is conservative, and cell size is a sign of stem cell function.”



Reference: Science Advances: Is the bigger the stem cell the better?


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