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Stem cells in the brain: limited self-renewal

Neuherberg, Germany, 06 March 2014. Stem cells in the brain can produce neurons and are consequently seen as a hope for treatment. A team of researchers from the Helmholtz Zentrum München and Ludwig-Maximilians-Universität München (LMU) has now discovered that the self-renewal rate of the stem cells is however limited, explaining why their number drops over the course of a lifetime. This work now sets the basis for further investigation of the signalling pathways that maintain the stem cells. The results have been published in the journal 'Nature Neuroscience'.

Stem cells in the brain: limited self-renewal

Image: A subclone of transiently amplifying progenitors in the subependymal zone. Source: J.Michel, ISF/Helmholtz Zentrum München

The generation of neurons (neurogenesis) in humans is predominantly limited to development; in the adult stage it takes place in only a few regions of the brain. These regions contain neural stem cells that generate neurons in a process with various intermediary stages.

Stem cell renewal is limited – total number drops

Until now it was thought that maintaining the stem cell pool was based on the self-renewal of individual stem cells. The team of scientists headed by Dr. Jovica Ninkovic and Professor Dr. Magdalena Götz were able to refute this: Both the self-renewal rate and the diversity of neurons formed from the stem cells are limited, and the number of stem cells decreases with age.

"Our findings explain why neurogenesis declines in later years, as there are fewer and fewer neural stem cells. At the same time, we gained new knowledge on basic mechanisms of neurogenesis that until now were not understood," says first author Dr. Filippo Calzolari.

Therapeutic approaches must focus on stem cells themselves

Approaches to new therapies for brain diseases, such as stroke or dementia, for example, particularly concentrate on replacing lost neurons by stimulating the generation of new cells from stem cells. "In light of the fact that the stem cell supply is limited, we must now also look for ways to promote the self-renewal rate of the stem cells themselves and maintain the supply for a longer time," emphasizes Götz, Director of the Institute for Stem Cell Research at the Helmholtz Zentrum München and Chair of the Institute of Physiological Genomics at LMU.

 

Further Information

Original publication:
Calzolari, F. et al. (2015). Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone. Nature Neuroscience, doi: 10.1038/nn.3963

Link to publication


The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.

The Institute of Stem Cell Research (ISF) investigates the basic molecular and cellular mechanisms of stem cell maintenance and differentiation. From that, the ISF then develops approaches in order to replace defect cell types, either by activating resting stem cells or by re-programming other existing cell types to repair themselves. The aim of these approaches is to stimulate the regrowth of damaged, pathologically changed or destroyed tissue.

As one of Europe's leading research universities, LMU Munich is committed to the highest international standards of excellence in research and teaching. Building on its 500-year-tradition of scholarship, LMU covers a broad spectrum of disciplines, ranging from the humanities and cultural studies through law, economics and social studies to medicine and the sciences. 15 percent of LMU‘s 50,000 students come from abroad, originating from 130 countries worldwide. The know-how and creativity of LMU's academics form the foundation of the University's outstanding research record. This is also reflected in LMU‘s designation of as a "university of excellence" in the context of the Excellence Initiative, a nationwide competition to promote top-level university research.

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Scientific contact
Prof. Magdalena Götz, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH),  Institute of Stem Cell Research, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel.: 089-3187-3750 -