Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stem Cells Can Become Anything – but Not Without This Protein

22.08.2012
How do stem cells preserve their ability to become any type of cell in the body? And how do they “decide” to give up that magical state and start specializing?

If researchers could answer these questions, our ability to harness stem cells to treat disease could explode. Now, a University of Michigan Medical School team has published a key discovery that could help that goal become reality.


Dou lab, University of Michigan

Mouse stem cells that have two normal copies of the Mof gene (left) function normally - but those with one or both copies malfunctioning lose their ability to self-renew (middle and right).

In the current issue of the prestigious journal Cell Stem Cell, researcher Yali Dou, Ph.D., and her team show the crucial role of a protein called Mof in preserving the ‘stem-ness’ of stem cells, and priming them to become specialized cells in mice.

Their results show that Mof plays a key role in the “epigenetics” of stem cells -- that is, helping stem cells read and use their DNA. One of the key questions in stem cell research is what keeps stem cells in a kind of eternal youth, and then allows them to start “growing up” to be a specific type of tissue.

Dou, an associate professor of pathology and biological chemistry, has studied Mof for several years, puzzling over the intricacies of its role in stem cell biology.

She and her team have zeroed in on the factors that add temporary tags to DNA when it’s coiled around tiny spools called histones. In order to read their DNA, cells have to unwind it a bit from those spools, allowing the gene-reading mechanisms to get access to the genetic code and transcribe it. The temporary tags added by Mof act as tiny beacons, guiding the “reader” mechanism to the right place.

“Simply put, Mof regulates the core transcription mechanism – without it you can’t be a stem cell,” says Dou. “There are many such proteins, called histone acetyltransferases, in cells – but only MOF is important in undifferentiated cells.”

Dou and her team also have published on another protein involved in DNA transcription, called WDR5, that places tags that are important during transcription. But Mof appears to control the process that actually allows cells to determine which genes it wants to read – a crucial function for stem-ness. “Without Mof, embryonic stem cells lost their self-renewal capability and started to differentiate,” she explains.

The new findings may have particular importance for work on induced pluripotent stem cells – the kind of stem cells that don’t come from an embryo, but are made from “adult” tissue.

IPCS research holds great promise for disease treatment because it could allow a patient to be treated with stem cells made from their own tissue. But the current way of making IPSCs from tissue involves a process that uses a cancer-causing gene – a step that might give doctors and patients pause.

Dou says that further work on Mof might make it possible to stop using that potentially harmful approach. But further research will be needed.

What they will focus on is how Mof marks the DNA structures called chromatin to keep parts of the genome readily accessible. In stem cells, scientists have shown, many areas of DNA are kept open for access – probably because stem cells need to use their DNA to make many proteins that keep them from ‘growing up.’

Once a stem cell starts to differentiate, or become a certain specialized type of cell, parts of the DNA close up and aren’t as accessible. Many scientific teams have studied this “selective silencing” and the factors that cause stem cells to start specializing by reading only certain genes. But few have looked at the factors that facilitate broad-range DNA transcription to preserve stem-ness.

“Mof marks the areas that need to stay open and maintains the potential to become anything,” Dou explains. Its crucial role in many species is hinted at by the fact that the gene to make Mof has the same sequence in fruit flies and mice.

“If you think about stem cell biology, the self-renewal is one aspect that makes stem cells unique and powerful, and the differentiation is another,” says Dou. “People have looked a lot at differentiation to make cells useful for therapy in the future – but the stem cell itself is actually pretty fascinating. So far, Mof is the only histone acetyltransferase found to support the stemness of embryonic stem cells.”

In addition to Dou, the research team includes her former postdoctoral fellow Xiangzhi Li, Ph.D., now at Shandong University in China; colleagues from the Department of Biostatistics and Bioinformatics in the Rollins School of Public Health at Emory University; and colleagues from the Laboratory of Gene Expression at the National Institutes of Health.

The work was funded by the National Institutes of Health (NIGMS R01GM082856 and NHGRI R01HG005119), the American Cancer Society, and by the National Natural Science Foundation of China.

Reference: Cell Stem Cell 11, 2 - 163–178, August 2012

For more information on stem cell research at U-M, visit www.stemcellresearch.umich.edu

Kara Gavin | Newswise Science News
Further information:
http://www.umich.edu
http://www.stemcellresearch.umich.edu

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton 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: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>