Swapping one sugar for another helps create 'super stem cells'

Swapping one sugar for another leads stem cells to become 'fitter and younger' versions of themselves, new research has revealed.

In a study performed by the University of Copenhagen, Denmark, mouse embryonic stem cells were grown in a cell culture medium containing D-galactose instead of the standard D-glucose. Swapping the sugars caused the cell's metabolism to switch from glycolysis, a fast but inefficient process, to oxidative phosphorylation, a more efficient but slower process, which led to improved cell health and versatility.

'We show that by changing their diet, the stem cells can rejuvenate and turn into "super stem cells",' said Dr Robert Bone, assistant professor at the Novo Nordisk Foundation Centre for Stem Cell Medicine at the University of Copenhagen, and first author of the study published in The EMBO Journal. 'It forces them to metabolise their energy in a different way than they normally would, and that process essentially reprogrammes the cells. The net result is that they behave like they are from an earlier stage of development, which enhances their ability to develop, or differentiate, into other types of cells.'

Stem cells are undifferentiated cells and have the potential to develop into any type of bodily cell, such as liver, skin or nervous cells. They are usually developed as cells from a mammal's embryo and grown ex vivo in a cell culture featuring a sugar-rich growth medium.

A key application of stem cells is improving fertility treatments, such as IVF. The inner cell mass, or embryoblast, is a mass of cells within the blastocyst during the early development of an embryo. Cells of the inner cell mass are pluripotent and can give rise to all three germ layers of the developing embryo, forming both embryonic and extra-embryonic tissue. The extra-embryonic tissues, such as the placenta and the yolk sac, are critical for an embryo to develop during pregnancy and are crucial for embryo implantation in the uterus.

'One of the things that the "super stem cells" seem to be better at making is a cell lineage that becomes something called the yolk sac. Previous research has found that the formation of the yolk sac in embryos cultured in a dish is very important for their ability to implant and become successful pregnancies,' said Dr Bone.

When the scientists changed the type of sugar in the medium the stem cells were grown in, they found that the cells were healthier and better at differentiating. Triggering oxidative phosphorylation activates specific enzymes to remove the acetyl groups from histones and transcription factors. This enables DNA with irrelevant genes to be more tightly coiled around the histones, while enabling more important genes to be exposed and thus expressed.

Furthermore, transcription factors with fewer acetyl groups can bind to target DNA sequences more accurately and express the desired genes without expressing unintended genes, referred to as transcriptional noise. The removal of transcriptional noise helps each stem cell express genes associated with differentiation into a specific cell lineage rather than expressing genes of different lineages.

Beyond aiding reproductive treatment, the researchers hope these rejuvenated stem cells could also play a key role in regenerative medicine, where damaged tissue is either repaired or replaced.

'Perhaps we could use this trick to regenerate aging cells and treat diseases such as Parkinson’s disease, osteoporosis or diabetes,' said Professor Joshua Brickman, from the Novo Nordisk Foundation Centre for Stem Cell Medicine, and corresponding author of the study.