Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Interaction between stem cells and their niches key to differentiation

26.01.2005


Duke University Medical Center cell biologists have defined a signaling system between stem cells and the specialized "niche cells" that harbor and regulate them. The findings provide better understanding of the signals that stimulate stem cells to either create more copies of themselves or to differentiate into another cell type, said the researchers.



Germline stem cells are immature cells in the reproductive system that can proliferate and mature into sperm and eggs. While it is has been appreciated that these stem cells exist in a microenvironment attached niche cells, it has not been well understood how these two cell types communicate.

In their latest study, the results of which were published in the Jan. 26, 2005, issue of the journal Current Biology, the Duke team reported that regulatory genes from niche cells instruct genes in stem cells to determine the future path of the stem cells. Both niche and stem cells possess genes which produce proteins that act as a series of "on-off" switches for stem cell division, the researchers said. The research was supported by the National Institutes of Health.


Over-proliferation of stem cells is one of the leading causes of cancer, while reduced stem cell production is implicated in such disorders as infertility, anemia and immune system deficiencies. It is important to understanding how stem cells receive their cues to differentiate, the researchers continued, because any potential future clinical application of stem cells cannot focus on them alone, but must also take into account the role of niche cells.

For their experiments, researchers led by Duke cell biologist Haifan Lin, Ph.D. studied germline stem cells from the ovaries of the common fruit fly Drosophila. They analyzed the expression of specific genes as the germline stem cells either created additional copies of themselves or differentiated into another cell type known as a cystoblast, which eventually become mature eggs. "We found that stem cells behavior is regulated by the neighboring niche cells, which provide an idyllic hideaway essential to the functioning of the stem cells," Lin said. "Stem cell division is an asymmetric process. After division, one daughter cell remains attached to the niche cell and thus remains as a stem cell, whereas the other daughter cells is detached from niche cells and will thus acquire a different fate."

Lin’s team determined three different genes -- piwi, pumilio (pum) and bam (bag of marbles) – that mediate the interplay between stem cells and niche cells that controls stem cell fate. It has been known that piwi and pum must be activated for successful self-renewal of germline stem cells, while bam is essential for cystoblast differentiation. Piwi, initially discovered in the Lin lab, is the founding member of a family of genes involved in the development stem cells in diverse organisms in both animal and plant kingdoms. pum- and bam-like genes also exist in mammals and humans. "In our experiments we demonstrated that piwi and bam proteins are expressed independently of each other in reciprocal patterns in germline stem cells and cystoblasts," Lin said. "However, overexpression of either one of these genes antagonizes the action of the other in these cells, acting as on-off switches."

According to their new model of niche cell-germline stem cell interaction, activation of the piwi gene in niche cells leads to the production of proteins that block the expression of bam in germline stem cells. The absence of an active bam gene causes pum, and other genes in the stem cells, to become active. The pum gene then prevents the production of proteins involved in differentiation. "The result of this sequence of events is the suppression of differentiation, which maintains the fate of the cell as a germline stem cell," Lin said.

In the cystoblast cell, the signal from piwi is no longer effective because this cell is detached from niche cells, which allows for the expression of the bam gene, which in turn represses the activity of pum, allowing the cell to differentiate. "Therefore, pum can be considered as the switch between self-renewal or differentiation, and signaling from niche cells through bam regulates this switch at the single cell level," Lin explained.

As they have done in their previous studies using the Drosophila model, Lin’s team is also using the mouse model to determine whether or not the same signaling pathways are present in higher organisms. Interestingly, they said, while the piwi gene plays an important role in determining germline stem cell differentiation in Drosophila, its equivalent in mice, miwi, has been shown to be the key gene involved in development of sperm cells. In humans, Lin’s team discovered in 2002 that overexpression of the hiwi gene, a piwi-like gene in human, has been implicated in the development of a common form of testicular cancer, while underexpression can lead to infertility.

First authors of the paper were Akos Szakmary, Ph.D., Duke, and Daniel Cox, Ph.D., now at George Mason University, Manassas, VA.

Richard Merritt | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>