Waiting to build new tissue - embryonic stem cell self control revealed
6th February 2007
Scientists think they’ve discovered a mechanism that helps to give embryonic stem cells their unique ability to develop into the many specialised cells that make up the human body. A cellular machine called the proteasome, which is responsible for breaking up protein molecules that are no longer needed by the cell, also helps to keep embryonic stem cells in a dynamic state so that they are ready to turn into different cell types.
Mouse embryonic stem cells can be grown in culture and used to study how stem cells are able to turn into different specialised tissues
Using embryonic stem cells from mice, cell development experts Professor Niall Dillon and Dr Henrietta Szutorisz of the MRC’s Clincial Sciences Centre have tackled the question of how embryonic stem cells stay poised for action. Their research shows that these cells have a novel way of blocking the normal process of DNA transcription whereby genetic instructions are copied from DNA.
Professor Dillon’s team discovered the role of the proteasome by experimenting with ways to hold back DNA transcription.
He explained: ‘‘A key feature of embryonic stem cells is their ability to activate many different gene expression programmes so that they can change into specialised cells. What we have discovered is that the gene expression machinery of embryonic stem cells is highly active, but it is not subject to the same level of regulation found in more specialised cells. Interestingly we also found that there is a lot of what is called ‘permissive’ DNA transcription going on. This means that instructions are copied from bits of DNA that wouldn’t normally be read. It seems that the proteasome continuously breaks up the proteins involved in permissive transcription whilst leaving normal DNA transcription unaffected.
He summarised: ‘‘By keeping the permissive transcription machinery of embryonic stem cells under control, the proteasome allows the cells to function, whilst maintaining their potential to give rise to different cell types. This kind of developmental flexibility is known as pluripotency.’’
Pluripotent embryonic stem cells exist for a short period in the early embryo, before they start to specialise and lose their ability to become many different cell types. In vitro, in the lab, they can renew themselves indefinitely in a petri dish and still maintain this flexibility.
Scientists have long wondered what it is about embryonic stem cells that allows them to develop into so many different cell types. Details of the cellular mechanisms needed to transform a stem cell into one that will eventually create skin, nerve cells, blood vessels or bone are key. This knowledge will fuel the medicine of regeneration that many scientists hope to develop from embryonic stem cells.
Professor Dillon concluded: ‘‘We are still far from understanding exactly how embryonic stem cells control their development into specific cell types, but the information that we have gained about the proteasome is one piece in the puzzle. The control afforded by the proteasome is likely to have the effect of keeping genes for specific body tissues poised and ready for activation if and when the cell differentiates.’’
Original paper: The proteasome restricts permissive transmission at tissue-specific gene loci. Published online in Cell on 29th December.
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