Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stowers Researchers Reveal Molecular Competition Drives Adult Stem Cells to Specialize

07.08.2014

Adult organisms ranging from fruit flies to humans harbor adult stem cells, some of which renew themselves through cell division while others differentiate into the specialized cells needed to replace worn-out or damaged organs and tissues.


Courtesy: Ting Xie, Ph.D., Stowers Institute for Medical Research

A bam mutant fruit fly ovary, known as the germanium, contains only adult stem cell-like cells (red) and spherical spectrosome (green). The accumulation of only adult stem cell-like cells indicates a mutation in the master differentiation factor bam completely blocks germline stem cell lineage differentiation.

Understanding the molecular mechanisms that control the balance between self-renewal and differentiation in adult stem cells is an important foundation for developing therapies to regenerate diseased, injured or aged tissue.

In the current issue of the journal Nature, scientists at the Stowers Institute for Medical Research report that competition between two proteins, Bam and COP9, balances the self-renewal and differentiation functions of ovarian germline stem cells (GSCs) in fruit flies (Drosophila melanogaster).

“Bam is the master differentiation factor in the Drosophila female GSC system,” says Stowers Investigator Ting Xie, Ph.D., and senior author of the Nature paper. “In order to carry out the switch from self-renewal to differentiation, Bam must inactivate the functions of self-renewing factors as well as activate the functions of differentiation factors.”

Bam, which is encoded by the gene with the unusual name of bag-of-marbles, is expressed at high levels in differentiating cells and very low levels in GSCs of fruit flies.

Among the self-renewing factors targeted by Bam is the COP9 signalosome (CSN), an evolutionarily conserved, multi-functional complex that contains eight protein sub-units (CSN1 to CSN8). Xie and his collaborators discovered that Bam and the COP9 sub-unit known as CSN4 have opposite functions in regulating the fate of GSCs in female fruit flies.

Bam can switch COP9 function from self-renewal to differentiation by sequestering and antagonizing CSN4, Xie says. “Bam directly binds to CSN4, preventing its association with the seven other COP9 components via protein competition,” he adds. CSN4 is the only COP9 sub-unit that can interact with Bam.

“This study has offered a novel way for Bam to carry out the switch from self-renewal to differentiation,” says Xie, whose lab uses a combination of genetic, molecular, genomic and cell biological approaches to investigate GSCs as well as somatic stem cells of fruit flies.

In the Nature paper, Xie’s lab also reports that CSN4 is the only one of the eight sub-units that is not involved in the regulation of GSC differentiation of female fruit flies. “One possible explanation for the opposite effects of CSN4 and the other CSN proteins is that the sequestration of CSN4 by Bam allows the other CSN proteins to have differentiation-promoting functions,” he says.

“As a powerful model system for studying adult stem cells, Drosophila female GSCs have revealed many novel regulatory strategies which have been later confirmed to be generally true,” adds Su Wang, a co-first author of the paper and also a graduate student in Department of Anatomy and Cell Biology at University of Kansas Medical Center.

In their future studies, Xie says that he hopes to identify the molecular mechanisms that enable COP9 with CSN4 to promote GSC self-renewal and without CSN4 to enhance differentiation.

The findings reported in Nature build upon previous research in Xie’s lab to understand the molecular mechanisms that influence GSC self-renewal and differentiation. The lab previously found that Bam is required to repress the expression of E-cadherin, a cell-to-cell adhesion molecule that tethers adult stem cells to their tissue niches and promotes GSC self-renewal.

Xie’s lab also has shown that Bam inactivates the function of another promoter of GSC self-renewal, the eukaryotic initiation factor-4A (eIF4A), which plays a role in gene expression. Xie points out that studies in other labs have revealed that Bam also suppresses the expression of the protein Nanos. Like COP9, Nanos is regarded as essential to establishing and maintaining self-renewing GSCs in female fruit flies.

In addition to Xie, other members of the Stowers team were first co-authors Lei Pan, Ph.D., and Su Wang, Ph.D., Changjiang Weng, Ph.D., Xiaoqing Song, and Junjing Yu. Also contributing were Jin Sun, Ph.D., Tinglin Lu, Zhi-Hao Yang, and Jianquan Ni, Tsinghua University, Beijing, China; Hong Tang, Ph.D., Chinese Academy of Sciences, Beijing; Joseph K. Park, M.D., Ph.D., and Dennis M. McKearin, Ph.D., University of Texas Southwestern Medical Center, Dallas, Texas; and Daniel A. Chamovitz, Ph.D., Tel Aviv University, Tel Aviv, Israel.

The Stowers Institute for Medical Research, National Natural Science Foundation of China (31370909) Ministry of Science and Technology of China (2012CB518900) and the National Institutes of Health (R01DC008003) funded the research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

About the Stowers Institute for Medical Research

The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife, Virginia, opened the Institute in 2000. Since then, the Institute has spent over one billion dollars in pursuit of its mission.

Currently, the Institute is home to nearly 550 researchers and support personnel; over 20 independent research programs; and more than a dozen technology-development and core facilities.

Contact Information

Kim Bland
ksb@stowers.org
Phone: 816-926-4015

Kim Bland | newswise

Further reports about: Cells Drosophila GSC Molecular female flies mechanisms proteins self-renewal

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>