Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enough is enough - stem cell factor Nanog knows when to slow down

25.11.2016

The transcription factor Nanog plays a crucial role in the self-renewal of embryonic stem cells. Previously unclear was how its protein abundance is regulated in the cells. Researchers at the Helmholtz Zentrum München and the Technical University of Munich, working in collaboration with colleagues from ETH Zürich, now report in ‘Cell Systems’ that the more Nanog there is on hand, the less reproduction there is.

Every stem cell researcher knows the protein Nanog* because it ensures that these all-rounders continue to renew. A controversial debate revolved around how the quantity of Nanog protein in the cell is regulated. "So far it was often assumed that Nanog activates itself in order to preserve the pluripotency in embryonic stem cells," explains Dr. Carsten Marr.


STILT generates simulated protein expression of dividing cells based on measured data and a dynamic model.

Source: Helmholtz Zentrum München


The authors Dr. Justin Feigelman and Dr. Carsten Marr

Source: Helmholtz Zentrum München

He heads the Quantitative Single Cell Dynamics research group at the Institute of Computational Biology (ICB) of the Helmholtz Zentrum München. Together with colleagues from ETH Zürich, he and his team have developed an algorithm called STILT (Stochastic Inference on Lineage Trees) that now rebuts this assumption.

Using STILT, the scientists evaluated time-resolved protein expression data (already collected in 2015) from individual cells in which Nanog could be detected through fusion with a fluorescence protein. "We compared the Nanog dynamics that were measured in this way with three different models. One of the challenges here was the quantitative comparison of the models, and another was taking stem cell divisions into account in the algorithm," reports first author Dr. Justin Feigelman, who had moved from the Helmholtz Zentrum München to ETH Zürich as a postdoc. "The results show that Nanog is regulated by a so-called negative feedback loop, which means that the more Nanog there is in the cells, the less reproduction there will be."

Carried over from the computer to the petri dish

In order to check these results, the scientists calculated what would happen if there were an artificial increase in Nanog protein levels. "We then actually succeeded in confirming the hypothesis put forward by STILT in an additional single-cell experiment with increased Nanog," explains study leader Marr.

Thanks to their research, the scientists promise a better understanding for stem cell renewal and hope that this knowledge might be useful for medical applications in the future. "We will also be applying STILT to other time-resolved single cell data in the future, which will give us insight into the underlying molecular gene regulation mechanisms," Marr explains.

The STILT software is freely available to other scientists on the Internet: http://www.imsb.ethz.ch/research/claassen/Software/stilt---stochastic-inference-on-lineage-trees.html

Further information

* The name is derived from Tír na nÓg, which is the "Land of Eternal Youth" according to an Irish legend. Among other jobs, Nanog is responsible for pluripotency, which is the ability that stem cells have to develop into almost any other cell type.

Background:
The data were collected in the framework of an already published study from 2015 that used thousands of individual cells (Filipczyk et al., 2015, Nature Cell Biology). At that time, the ICB scientists were already able to draw unexpected conclusions regarding the regulatory network involving Nanog. http://www.helmholtz-muenchen.de/en/press-media/press-releases/2015/press-release/article/27689/index.html

Original Publication:
Feigelman, J. et al. (2016): Exact Bayesian lineage tree-based inference identifies Nanog negative autoregulation in mouse embryonic stem cells. Cell Systems, doi: 10.1016/j.cels.2016.11.001
http://dx.doi.org/10.1016/j.cels.2016.11.001


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

The Institute of Computational Biology (ICB) develops and applies methods for the model-based description of biological systems, using a data-driven approach by integrating information on multiple scales ranging from single-cell time series to large-scale omics. Given the fast technological advances in molecular biology, the aim is to provide and collaboratively apply innovative tools with experimental groups in order to jointly advance the understanding and treatment of common human diseases. http://www.helmholtz-muenchen.de/icb

Technical University of Munich (TUM) is one of Europe’s leading research universities, with more than 500 professors, around 10,000 academic and non-academic staff, and 40,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, com-bined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany. http://www.tum.de/en/homepage

Freedom and individual responsibility, entrepreneurial spirit and open-mindedness: ETH Zurich stands on a bedrock of true Swiss values. Our university for science and technology dates back to the year 1855, when the founders of modern-day Switzerland created it as a centre of innovation and knowledge. At ETH Zurich, students discover an ideal environment for independent thinking, researchers a climate which inspires top performance. Situated in the heart of Europe, yet forging connections all over the world, ETH Zurich is pioneering effective solutions to the global challenges of today and tomorrow. Some 500 professors teach around 20,000 students – including 4,000 doctoral students – from over 120 countries. Their collective research embraces many disciplines: natural sciences and engineering sciences, architecture, mathematics, system-oriented natural sciences, as well as management and social sciences. The results and innovations produced by ETH researchers are channelled into some of Switzerland’s most high-tech sectors: from computer science through to micro- and nanotechnology and cutting-edge medicine. Every year ETH registers around 90 patents and 200 inventions on average. Since 1996, the university has produced a total of 330 commercial spin-offs. ETH also has an excellent reputation in scientific circles: 21 Nobel laureates have studied, taught or researched here, and in international league tables ETH Zurich regularly ranks as one of the world’s top universities. http://www.ethz.ch/en.html


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:
Dr. Carsten Marr, Helmholtz Zentrum München - German Research Center for Environmental Health, Institute of Computational Biology, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel. +49 89 3187 2158, E-mail: carsten.marr@helmholtz-muenchen.de

Weitere Informationen:

http://www.helmholtz-muenchen.de/en/press-media/press-releases/2016/index.html - more press releases of Helmholtz Zentrum München

Sonja Opitz | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

More articles from Life Sciences:

nachricht Microbes can grow on nitric oxide (NO)
18.03.2019 | Max-Planck-Institut für Marine Mikrobiologie

nachricht Novel methods for analyzing neural circuits for innate behaviors in insects
15.03.2019 | Kanazawa University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Revealing the secret of the vacuum for the first time

New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum

For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...

Im Focus: Sussex scientists one step closer to a clock that could replace GPS and Galileo

Physicists in the EPic Lab at University of Sussex make crucial development in global race to develop a portable atomic clock

Scientists in the Emergent Photonics Lab (EPic Lab) at the University of Sussex have made a breakthrough to a crucial element of an atomic clock - devices...

Im Focus: Sensing shakes

A new way to sense earthquakes could help improve early warning systems

Every year earthquakes worldwide claim hundreds or even thousands of lives. Forewarning allows people to head for safety and a matter of seconds could spell...

Im Focus: A thermo-sensor for magnetic bits

New concept for energy-efficient data processing technology

Scientists of the Department of Physics at the University of Hamburg, Germany, detected the magnetic states of atoms on a surface using only heat. The...

Im Focus: The moiré patterns of three layers change the electronic properties of graphene

Combining an atomically thin graphene and a boron nitride layer at a slightly rotated angle changes their electrical properties. Physicists at the University of Basel have now shown for the first time the combination with a third layer can result in new material properties also in a three-layer sandwich of carbon and boron nitride. This significantly increases the number of potential synthetic materials, report the researchers in the scientific journal Nano Letters.

Last year, researchers in the US caused a big stir when they showed that rotating two stacked graphene layers by a “magical” angle of 1.1 degrees turns...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Researchers measure near-perfect performance in low-cost semiconductors

18.03.2019 | Power and Electrical Engineering

Nanocrystal 'factory' could revolutionize quantum dot manufacturing

18.03.2019 | Materials Sciences

Long-distance quantum information exchange -- success at the nanoscale

18.03.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>