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A trifling paper cut has a lot of activity. A squad of stem cells quickly regenerate to patch up the wound. Some of the stem cells are native to the area, but others are newcomers that migrate from the hair follicle to the wound bed.
A new study shows that stem cells that have been relocated retain memories of how to travel from the follicle to the skin's surface, repair damaged skin, and finally adapt to their new home. These seasoned stem cells are very different from naive stem cells. According to the new research, they are primed to heal wounds faster, and after repeated wounds, may develop memories that could lead to chronic disease and cancer.
Elaine Fuchs says that normal stem cells look the same as hair follicle-derived stem cells. The memory of their migration has consequences.
Beyond inflammatory memory.
In recent years, scientists have found that immune cells can acquire epigenetic changes when fighting off pathogens, sensitizing them to further inflammation in a process known as trained or inflammatory memory.
In order to understand some of the mysteries surrounding atopic dermatitis and chronic wounding, Fuchs and colleagues began investigating inflammatory memory in skin. They found that stem cells can use memories of inflammation to muster non-specific, short-term responses to injury and inflammation.
T cells and B cells of the immune system used to be thought of as a privilege. Our findings show that it's more widespread.
This means that the skin will heal faster if it is damaged a second time. The bookmarking reminds each cell which genes it had to silence to defeat a previous challenge, empowering it to respond more efficiently to future injuries. Inflammation has been found in the airway and the gut, with implications for asthma and inflammatory bowel disease.
Minor everyday skin injuries were the focus of the study. Sixty days after the injury, they found that the mouse's stem cells were able to remember inflammation and learn how to heal wounds. The stem cells that were abandoned the hair follicles to rise to the surface and maintain the skin's inner layer contained a number of markers in their genetic material that are not seen in run-of-the-mill trained immunity. Stem cells were given flexibility because of their previous and current jobs. The immigrant stem cells were able to mobilize more efficiently than native stem cells because of their memories of their migration to the skin's surface.
The wide diversity of memories that stem cells can retain surprised the first author on the study. Stem cells can potentially remember other things as well as the inflammation they have been shown to record, according to our experiments.
Bad memories.
Epigenetic memory may lead to chronic disease, and fast wound repair is usually a good thing. "We know that tumors often arise at sites of previous injury, and that inflammatory bouts of Psoriasis often occur on the same sites." "This suggests that the diversity of memories accumulated over time could be a factor in chronic diseases that arise later in life."
The equivalent of five or six years of human life can be had by mice with potentially dangerous stem-cell memories. It happens to most of us at least once a week. It is likely that these memories came from evolution to help animals heal wounds faster. Humans live longer, and it's disconcerting to think that we develop long lasting memories of our injuries and exposure to pathogens.
This recent study contributes to a larger body of work that is teaching scientists about a bunch of inflammatory diseases, many of which develop in the epithelial tissues that are our first line of defense from the outside world. There is mounting evidence that suppressing the immune system may not target the roots of the problem, and so the prevailing treatment for chronic inflammatory disorders of these epithelial tissues are immunosuppressive drugs.
In the future, Fuchs hopes to provide better treatment alternatives by drilling down to the fundamental mechanisms behind the formation of maladaptive stem-cell memories. We would eventually be able to get rid of bad memories and keep the good ones. New discoveries have created an explosion of interest in a broad variety of research fields, and are already guiding us toward novel approaches to treating disease.
Kevin Andrew Uy Gonzales and his team show how Stem cells can alter tissue fitness by accumulating diverse epigenetic memories. There is a science.abh2444
Science journal information.
Stem cell memories may drive wound repair and chronic disease.
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