Interesting Science

'Epigenetics to shape stem cell future' and 'Cancer is a stem cell issue':

1) Epigenetics to shape stem cell future

Everyone hopes that one day stem cell-based regenerative medicine will help repair diseased tissue. Before then, it may be necessary to decipher the epigenetic signals that give stem cells their unique ability to self-renew and transform them into different cell types.

The hype over epigenetic research is because it opens up the possibility of reprograming cells. By manipulating epigenetic marks, cells can be transformed into other cell types without changing their DNA. It is simply a question of adding or removing the chemical tags involved.

Stem cells rely heavily on epigenetic signals. As a stem cell develops, chemical tags on the DNA or its surrounding histone proteins switch genes on or off, controlling a cell's fate.

European labs are breaking ground in both the epigenetic and stem cell arenas. To build on this expertise and stimulate the exchange on novel technologies, the European Science Foundation organised the EuroSTELLS workshop 'Exploring chromatin in stem cells' [Chromatin]. The event held on 23- 24 January, 2007 attracted 106 researchers from 15 countries to Montpellier, France.

"Epigenetics and stem cell biology are such clear strengths in the European research community," remarked Bradley Bernstein, a guest speaker from Massachusetts General Hospital, Boston. "We've found ourselves working very hard in the US to catch up."

Epigenetic research has benefited tremendously from genome technology, and work in the field is advancing at break-neck speed. "If you think that the first enzymes controlling histone methylation were found in 2001, the acceleration is tremendous," says Robert Feil, a EuroSTELLS researcher based at the CNRS Institute of Molecular Genetics in Montpellier. "We are making good use of past investments in genome sequencing. In the next five years the technology will be ten times faster than it has been so far."

Conference goers reported that new high-throughput approaches and refined analytical techniques promise to fill in some big gaps in understanding how epigenetic tags define a stem cell and how they can be manipulated. With this knowledge on board, researchers will be boosting the odds that one day stem cell therapies will reach the clinic.

EuroSTELLS is the European Collaborative Research (EUROCORES) programme on "Development of a Stem Cell Tool Box" developed by the European Science Foundation.

Source: European Science Foundation PR February 19th 2007

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2) Cancer is a stem cell issue

There is an urgent reason to study stem cells: stem cells are at the heart of some, if not all, cancers. Mounting evidence implicates a clutch of rogue stem cells brandishing 'epigenetic' marks as the main culprits in cancer. Wiping out tumours [tumors] for good, some biologists believe, depends on uprooting these wayward stem cells.

A team in the Netherlands has uncovered a key protein that could stop these stem cells from becoming malignant. "This is a hot topic in the cancer field," Maarten van Lohuizen of The Netherlands Cancer Institute, Amsterdam told participants at a EuroSTELLS workshop, held in Montpellier, France, 23-24 January. "To be successful in cancer therapy you need to target these stem cells: they are intrinsically resistant to chemotherapy."

Polycomb proteins have emerged as key players in cancer pathogenesis. They are powerful epigenetic regulators that normally silence genes without altering the cell's DNA. Compounds that regulate polycomb could result in novel anticancer drugs that shrink malignant tissue, and prevent cancer recurrence, a common problem with most chemotherapies.

That tumours and stem cells have much in common has been known for many years. Both self-renew and both spawn many different types of cells. But only recently, new techniques have enabled biologists to identify stem cells buried in tumours.

Van Lohuizen has found that stem cells in cancerous tissues are locked in an immature state in which they carry on multiplying instead of maturing into specific tissues. "Some resistant cancer cells don't listen to the 'stop' signal any more," he explains. That stop sign is delivered by the polycomb proteins. They silence several genes at once by affecting the way the DNA is compacted into chromatin fibres, without altering the DNA sequence.

Normally, the main role of the polycomb complex is to repress genes during development or when stem cells are needed for tissue maintenance. But an aberrant polycomb spells trouble. In mice where polycomb proteins have been genetically disabled, van Lohuizen has seen that the cells become invasive and trigger cancerous growth. "This may be why gliomas are such lethal tumours, because these stem cells become highly migratory," van Lohuizen points out.

The hunt is now on for therapeutic agents that target these budding cancer stem cells. The Dutch researcher is optimistic that used in combination with chemotherapy, such compounds will also prevent cancer reigniting after treatment. "We have to be very careful because [these compounds] will also regulate normal stem cell behaviour. It is a fine balance," he noted.

EuroSTELLS is the European Collaborative Research (EUROCORES) programme on "Development of a Stem Cell Tool Box" developed by the European Science Foundation.

Source: European Science Foundation PR February 19th 2007

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