Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

MDC Scientists Show How Hematopoietic Stem Cell Development Is Regulated

06.10.2009
During cell division, whether hematopoietic stem cells (HSCs) will develop into new stem cells (self-renewal) or differentiate into other blood cells depends on a chemical process called DNA methylation.

These were the findings of researchers at the laboratory of Dr. Frank Rosenbauer of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch in cooperation with the laboratory of Professor Sten Eirik W. Jacobsen (Lund University, Sweden and the University of Oxford, England). Furthermore, the researchers showed that DNA methylation also plays a crucial role for cancer stem cells (Nature Genetics, online, doi: doi:10.1038/ng.463)*.

A group of three enzymes, the DNA methyltransferases (Dnmt) regulates the addition of methyl groups to the DNA (DNA methylation). One of these enzymes - Dnmt1 - is responsible for the maintenance of the marks with the methyl groups, the DNA methylation pattern, because the distribution of the methyl groups on the DNA decides which genes are transcribed and which are blocked. Researchers speak in this context of epigenetic information, in contrast to genetic information.

However, it was unclear until now whether DNA methylation plays a special role in the control of hematopoietic stem cell characteristics. From the HSCs all of the blood cells of the body are formed. Since blood cells have only a limited lifetime, the body must form new blood cells over and over again. The pool for this is generated by the HSCs.

In order to discover what function DNA methylation has for HSCs, the two doctoral students Ann-Marie Bröske and Lena Vockentanz of the MDC research laboratory of Dr. Rosenbauer switched off the enzyme Dnmt1 in the mice. As a result, the animals were not viable because the hematopoietic stem cell function was completely disturbed.

By contrast, when the two researchers arranged that the HSCs formed just a little Dnmt1, the animals survived, but the HSCs lost their potential for self-renewal. Moreover, the HSCs were restricted in their formation of B cells and T cells (blood cells of the lymphatic system and important cells of the immune system).

However, the HSCs were able to form red blood cells, which are important for oxygen transport and belong to the blood cells of the myeloerythroid system. In other words, the DNA methylation level regulates which blood cell lineages develop or not from a hematopoietic stem cell.

Cancer stem cells
Methylation processes also play a role in numerous cancer diseases. As the MDC researchers were able to show, the DNA methylation by the enzyme Dnmt1 also controls the development of leukemic stem cells.

If the DNA methylation level is low, cancer stem cell renewal is restricted. Moreover, the formation of leukemic cells of B-cell lineage (acute B-cell leukemia - ALL) is blocked.

The question is whether diseased stem cells can be switched off, possibly through a blockade of the enzyme Dnmt1. Dr. Rosenbauer and his research team want to make a more detailed investigation of this question in a further project.

*DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction
Ann-Marie Bröske1*, Lena Vockentanz1*, Shabnam Kharazi2, Matthew R. Huska1, Elena Mancini3, Marina Scheller1, Christiane Kuhl1, Andreas Enns1, Marco Prinz4, Rudolf Jaenisch5, Claus Nerlov3, Achim Leutz1, Miguel A. Andrade-Navarro1, Sten Eirik W. Jacobsen2,6 and Frank Rosenbauer1
1 Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
2 Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
3 European Molecular Biology Laboratory, Mouse Biology Unit, Monterotondo, Italy
4 Department of Neuropathology, University of Freiburg, Freiburg, Germany
5 The Whitehead Institute, 9 Cambridge Center, Cambridge, MA, USA
6 Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, England.

*These authors contributed equally to this work.

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10
13125 Berlin, Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | Max-Delbrück-Centrum
Further information:
http://www.mdc-berlin.de/
http://www.medfak.lu.se/stemcellcenter/hemat_stc_lab.htm

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>