New mechanisms regulating neural stem cells

February 21, 2019

The use of stem cells to repair organs is one of the foremost goals of modern regenerative medicine. Scientists at Helmholtz Zentrum München and Ludwig Maximilian University of Munich (LMU) have discovered that the protein Akna plays a key role in this process. It controls, for example, the behavior of neural stem cells via a mechanism that may also be involved in the formation of metastases. The study was published in the renowned journal 'Nature'.

The research team led by Prof. Dr. Magdalena Götz, director of the Institute for Stem Cell Research (ISF) at Helmholtz Zentrum München and Chair of Physiological Genomics of the LMU Biomedical Center, wanted to identify the factors that regulate the maintenance or differentiation of neural stem cells. To this end, the scientists isolated neural stem cells, which either self-renew and generate additional neural stem cells or differentiate. "We found that the Akna protein* is present in higher concentrations in stem cells that generate neurons," explains ISF researcher German Camargo Ortega, first author of the study together with Dr. Sven Falk. "Our experiments showed that low levels of the Akna protein cause stem cells to remain in the stem cell niche, whereas higher levels stimulate them to detach from the niche, thus promoting differentiation," the author continues.

The scientists were surprised to discover the position of the protein ? namely at the centrosome, an organelle in the cell's interior that acts as chief architect for the organization of the cytoskeleton and regulates cell division. "We discovered that an incorrect sequence was originally published for this protein," Sven Falk reports. "However, our work clearly showed that Akna is located directly at the centrosome." The researchers were able to show that Akna recruits and anchors microtubules at the centrosome. This weakens the connections to neighboring cells, and promotes detachment and migration from the stem cell niche.

"Our experiments show that this function also plays an important role in a process known as epithelial-to-mesenchymal transition, or EMT for short**", explains the study leader Magdalena Götz. "In this process, cells detach from a cluster, proliferate and begin to migrate. This occurs, for example when stem cells migrate to form new neurons, but it can also be harmful in disease, for example when cancer cells leave a tumor to form metastases elsewhere in the body. "The novel mechanism that we identified by studying the function of Akna therefore appears to play a key role in a broad range of medically relevant processes." In the next step, the research team plans to investigate the role of Akna in other stem cells and in the immune system.
-end-
Further Information

* The Akna protein is an AT hook transcription factor. A transcription factor is a protein that binds to DNA and regulates the transcription of one or more genes.

** Epithelial-to-mesenchymal transition (EMT) denotes a transition from epithelial cells (e.g. skin, gland tissues or mucous membranes) into cells with mesenchymal properties. Mesenchyma is developing tissue showing a high rate of cell division.

Original Publication:

Germán Camargo Ortega et al (2019): The centrosome protein Akna regulates neurogenesis via microtubule organization. Nature, DOI: 10.1038/s41586-019-0962-4

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, allergies 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. http://www.helmholtz-muenchen.de/en

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. http://www.helmholtz-muenchen.de/en/isf

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. http://www.en.lmu.de

Contact for the media:

Department of Communication, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel. +49 89 3187 2238 - Fax: +49 89 3187 3324 - E-mail: presse@helmholtz-muenchen.de

Scientific Contact:

Prof. Dr. Magdalena Götz, Helmholtz Zentrum München - German Research Center for Environmental Health, Institute of Stem Cell Research, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel. +49 89 3187 3750 - E-mail: magdalena.goetz@helmholtz-muenchen.de

Helmholtz Zentrum München - German Research Center for Environmental Health

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.