Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Back to sleep: How SETD1A takes blood stem cells to rest

08.05.2018

In old age, humans increasingly suffer from infections. Blood stem cells that are usually inactive are activated in order to produce as many blood and immune cells as needed to fight the infection. But every cell division entails the risk of accumulating DNA damages. Damaged cells are usually detected and eliminated, but if all stem cells are gone, there will be no cells to defend the body during the next infection. Researchers from Leibniz Institute on Aging (FLI) in Jena have identified a central mechanism related to SETD1A enzyme, which is responsible for detecting and repairing DNA damages in blood stem cells and, hence, is crucial for blood stem cells go back to sleep after infections.

Stem cells are our body’s emergency reserve. In the blood system, so-called hematopoietic (blood) stem cells are responsible for continuously producing immune cells. This process, called hematopoiesis, is strictly regulated to make sure that the number of produced cells correlates to the actual need. However, every cell division also entails the risk of DNA damage accumulation that may result in loss of function and possibly even in cancerogenic transformation – the development of cancer.


The enzyme SETD1A hinders the accumulation of DNA damages and, hence, helps blood stem cells to return to their resting phase to avoid attrition.

(Picture: FLI / K. Wagner; Source: among others, Fotolia and Panthermedia)

This is why stem cells usually rest in so-called quiescence to avoid attrition. During an infection, the number of immune cells needed is heavily rising, forcing blood stem cells to be activated in order to replicate and generate new immune cells. Subsequently, blood stem cells fall back to rest. In old organisms, this process is impaired because the accumulation of DNA damage increases over repeated cycling activity.

Damaged cells are detected via a sensory system and are removed, which may result in the continuous reduction of the size of the available stem cell pool. So far, it was known that particular DNA repair pathways are necessary to repair DNA damages. However, it was totally unclear how DNA repair pathways are activated.

Together with other scientists from Dresden, Heidelberg and Berlin, Prof. Dr. Claudia Waskow – Senior Group Leader at Leibniz Institute on Aging (FLI) in Jena, Germany and at Technical University Dresden, Germany, holding a professorship at Friedrich Schiller University in Jena as well – and her team have identified an epigenetic mechanism, which in mice regulates the activation of the DNA damage response in blood stem cells and, thus, helps them back into their quiescence. Results have been published in Journal Blood.

SETD1A: An epigenetic sleeping aid

Biologist and aging researcher Waskow and her team found histone-3-lysine-4-methyletransferase SETD1A to regulate the activation of all known DNA repair pathways by means of a so-called epigenetic histone modification. These epigenetic switches work by adding defined molecular entities to particular gene segments, thus ‘marking’ this gene and making it available for being read. This is how SETD1A regulates whether gene segments, which are responsible for repairing DNA damages of blood stem cells, are activated or not.

SETD1A was identified as the main driver of labeling the molecular groups and providing the whole repair machinery in blood stem cells, a process that is pivotal for the organism: In mice that lacked this genetic modifier, blood stem cells that had been activated during an infection, could not return to quiescence anymore. Blood stem cells accumulated DNA damages preventing the generation of mature immune cells, which resulted in a dramatically reduced survival rate after infection.

It may be possible to shorten the critical phase after infections

“The number of specific functions of SETD1A is really surprising”, explains Prof. Dr. Claudia Waskow. “Not only does SETD1A activity regulate the detection of DNA-damage in blood stem cells, but it also controls their repair. Simply spoken, SETD1A is crucial for the maintenance of blood stem cells”. If DNA damages in stem cells can be repaired fast and properly, they can go back to their resting phase more quickly, and further attrition can be avoided. This is how blood stem cells can be maintained to be available for reactivation during the next infection.

Since the repair mechanisms of SETD1A are based on epigenetic modifications, it may be possible to chemically control SETD1A activity. This can potentially provide a future approach for a supportive treatment after infections. “Especially in elderly people with a weaker immune system, the controlled increase of SETD1A activity could affect the return of blood stem cells back to quiescence in a positive way to maintain them for the next infection”, Prof. Waskow concludes.

Publication

Kathrin Arndt*, Andrea Kranz*, Juliane Fohgrub, Adrien Jolly, Anita S. Bledau, Michela Di Virgilio, Mathias Lesche, Andreas Dahl, Thomas Höfer, A. Francis Stewart and Claudia Waskow. SETD1A protects HSCs from activation-induced functional decline in vivo. Blood. 2018, 131(12), 1311-1324. doi: 10.1182/blood-2017-09-806844. (*equal contribution)

Contact

Dr. Kerstin Wagner
Press & Public relations
phone: +49 3641 656378
e-mail: presse@leibniz-fli.de

Background information

The Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) is the first German research organization dedicated to biomedical aging research since 2004. More than 330 members from over 30 nations explore the molecular mechanisms underlying aging processes and age-associated diseases. For more information, please visit http://www.leibniz-fli.de.

The Leibniz Association connects 93 independent research institutions that range in focus from the natural, engineering and environmental sciences via economics, spatial and social sciences to the humanities. Leibniz Institutes address issues of social, economic and ecological relevance. They conduct knowledge-driven and applied basic research, maintain scientific infrastructure and provide research-based services. The Leibniz Association identifies focus areas for knowledge transfer to policy-makers, academia, business and the public. Leibniz Institutes collaborate intensively with universities – in the form of “WissenschaftsCampi” (thematic partnerships between university and non-university research institutes), for example – as well as with industry and other partners at home and abroad. They are subject to an independent evaluation procedure that is unparalleled in its transparency. Due to the institutes’ importance for the country as a whole, they are funded jointly by the Federation and the Länder, employing some 19,100 individuals, including 9,900 researchers. The entire budget of all the institutes is approximately 1.9 billion EUR. See http://www.leibniz-association.eu for more information.

Weitere Informationen:

http://www.leibniz-fli.de - Website Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) Jena

Dr. Kerstin Wagner | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Purdue cancer identity technology makes it easier to find a tumor's 'address'

16.11.2018 | Health and Medicine

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>