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 Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>