Cambridge learns how to rewire stem cells

New technology developed by Cambridge UK researchers could rewire stem cells and help fight conditions such as heart & liver disease as well as cancer.

The fast-working technique determines what causes stem cells to convert into other cell types and could revolutionise understanding of how genes function.

The method uses stem cells with a single set of chromosomes, instead of the two sets found in most cells, to reveal what causes the circuitry of stem cells to be rewired as they begin the process of conversion into other cell types. The same method could also be used to understand a range of biological processes.

Embryonic stem cells rely on a particular gene circuitry to retain their original, undifferentiated state, making them self-renewing. The dismantling of this circuitry is what allows stem cells to start converting into other types of cells - a process known as cell differentiation - but how this happens is poorly understood.

The method uses stem cells with a single set of chromosomes to uncover how cell differentiation works.

Cells in mammals contain two sets of chromosomes one set inherited from the mother and one from the father. This can present a challenge when studying the function of genes, however: as each cell contains two copies of each gene, determining the link between a genetic change and its physical effect, or phenotype, is immensely complex.

The conventional approach is to work gene by gene, and in the past people would have spent most of their careers looking at one mutation or one gene, said Dr Martin Leeb, who led the research, in collaboration with Professor Austin Smith.

Today, the process is a bit faster, but its still a methodical gene by gene approach because when you have an organism with two sets of chromosomes thats really the only way you can go.

Dr Leeb used unfertilised mouse eggs to generate embryonic stem cells with a single set of chromosomes, known as haploid stem cells. These haploid cells show all of the same characteristics as stem cells with two sets of chromosomes, and retain the same full developmental potential, making them a powerful tool for determining how the genetic circuitry of mammalian development functions.

The researchers used transposons jumping genes to make mutations in nearly all genes. The effect of a mutation can be seen immediately in haploid cells because there is no second gene copy.

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Cambridge learns how to rewire stem cells