Nav: Home

Role model stem cells: How immune cells can self-renew

January 21, 2016

When our organs age or wear out, their renewal usually depends on a few stem cells in the tissue, because the vast majority of differentiated cells have lost their ability to divide and generate new cells. A German-French team led by Michael Sieweke from the Max Delbrück Center for Molecular Medicine (MDC) in Berlin and the Centre d'Immunologie de Marseille-Luminy (CIML) in Marseille has now discovered how human macrophages, a type of specialized immune cell, can nevertheless divide and self-renew almost indefinitely. As the researchers show in the journal Science, the macrophages achieve this by activating a gene network similar to one found in embryonic stem cells. In the future the findings could provide new directions in regenerative medicine and therapies.

Our body is constantly changing: new cells continually replace specialized cells to maintain the skin, intestine, blood, and other tissues or repair them after an injury. Since differentiated cells are usually no longer able to divide, the renewal is almost always accomplished by stem cells specific to the tissue, which are capable of continually generating new cells. Recently researchers have discovered some exceptions: some types of immune cells which have already differentiated possess a capacity for self-renewal.

Macrophages, which play an important role in immune defenses, can also control tissue regeneration and renewal.

A few years ago, a team led by German immunologist and stem cell researcher Michael Sieweke at the French CIML showed that under certain conditions macrophages can divide without losing features they have acquired while specializing into immune cells. The researchers had shown in mice that proteins that regulate the reading of genes, called transcription factors, play a decisive role in this process. Genetic manipulations that turned off two transcription factors named MafB and c-Maf in the macrophages caused the cells to start what appeared to be a self-renewal program. They could even be maintained and expanded almost indefinitely in cell cultures - which is usually not possible with differentiated cells.

In the new study, Sieweke's research team from the MDC in Berlin and the CIML in France have now been able to show that this also works with various macrophages taken from mice that have not undergone genetic manipulations. This happened when concentrations of both MafB and c-Maf were naturally low or were inhibited for a short time.

"We now asked ourselves how this is possible - in other words, what mechanisms and genes allow the differentiated macrophages to switch on self-renewal?" Sieweke says. To find out the researchers compared the macrophages to embryonic stem cells, which have a similar, unlimited capacity for self-renewal. The scientists compared the patterns of gene regulatory elements and genes that were active in the two types of cells.

"As it turned out, the macrophages contain a set of dormant genes that can be reawakened and thus enable self-renewal," Sieweke says. In this context, the researchers made a surprising discovery: the macrophage genes work together in a network very similar to one that is switched on in proliferating embryonic stem cells. "You could say that the differentiated cells contain dormant stem cell genes," Sieweke explains.

While the gene networks in the two types of cells are very similar, they are managed in different ways: they are controlled by different transcription factors and gene regulatory elements which are specific to each type of cell. "But it is good news to discover that macrophages can activate the self-renewal genes found in stem cells using their own very specific regulatory factors ," Sieweke says.

He believes that these findings will ultimately be useful in regenerative medicine. "If differentiated cells could be expanded directly, it might be possible to replace diseased tissue without taking a detour via embryonic or induced pluripotent stem cells," Sieweke says. He adds that the dormant gene network may also be activated in other types of cells - mature liver cells, for example, have the ability to divide as well.

Transplantation studies with macrophages suggest that such transplantations of macrophages might indeed be useful for regeneration. Sieweke's teams have already shown that macrophages grown in laboratory cultures do not lose their properties. When injected into mice, the cells successfully re-integrate into tissues and perform all of their normal functions. The cells are not only able to fight infections, but also have an important function in maintaining tissues and are needed for regeneration. "They are, so to speak, the gardeners or guardians of the tissue," Sieweke explains.
-end-
E. L. Soucie et al., Science 10.1126/science.aad5510 (2016)

Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells

Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Related Stem Cells Articles:

A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
New research finds novel method for generating airway cells from stem cells
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Mature heart muscle cells created in the laboratory from stem cells
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
Mutations in bone cells can drive leukemia in neighboring stem cells
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
More Stem Cells News and Stem Cells Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Teaching For Better Humans
More than test scores or good grades — what do kids need to prepare them for the future? This hour, guest host Manoush Zomorodi and TED speakers explore how to help children grow into better humans, in and out of the classroom. Guests include educators Olympia Della Flora and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...