Sanger maps unique route to stem cells

Cambridge researchers have developed a new method to produce stem cells using designed proteins.

Stem cells have the potential to be used to replace dying or damaged cells with healthy cells. This repair could have wide-ranging uses in medicine such as organ replacement, bone replacement and treatment of neurodegenerative diseases. This study brings closer to realising the full potential of stem cell technology.

We have gone down a completely different road to standard practices to produce stem cells from adult cells, says Dr Pentao Liu, senior author from the Wellcome Trust Sanger Institute.

Current techniques to reprogramme cells are inefficient and its imperative to find other ways to create stem cells. We hope that our novel approach to reprogramming cells into stem cells will become a new and safer alternative to current practices.

The team looked at proteins called transcription factors, which regulate the activity of all human genes. Each transcription factor acts to modify the activity of several or many genes.

A key set of these transcription factors are able to convert or reprogramme adult cells into induced pluripotent stem cells or iPS cells. However, these factors also act on many genes other than those involved in reprogramming.

The team developed artificial designer transcription factors to target those key reprogramming genes more accurately, minimising activity on other genes.

"This is a promising and exciting development in our attempt to produce iPS cells that lend themselves in practical applications, says Dr Xuefei Gao, first author from the Wellcome Trust Sanger Institute. We have shown that targeting gene-control regions, called enhancers, in this structured way is a very effective in controlling a gene and reprogramming cells to become iPS cells.

In conventional methods, the transcription factors used to programme cells take part in complicated ways and target many different parts of the genome as they are used to reprogramme the cells to become stems cells. As a result, the throughput of successfully reprogrammed cells can be low and the additional number of steps can have associated risks, such as affecting genes that can influence tumour development.

The designer transcription factors are extremely accurate. Because this method targets key genes directly and avoids additional genetic detours, it reduces the potential risks linked with standard practices.

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Sanger maps unique route to stem cells