Sleep deficit causes changes to epigenome of immune stem cells

Insufficient sleep changes the epigenome of immune stem cells leading to increasing inflammation within the body, new research suggests.

The study performed by Icahn School of Medicine, Mount Sinai, New York, examined haematopoietic stem cells (HSCs), found within bone marrow which undergo differentiation to form various types of white blood cell responsible for mounting a body's immune response. Researchers found that shortened sleep can lead to changes in the epigenome of HSCs, leading to a reduction in diversity of stem cells and an overproduction of certain white blood cells, called monocytes, triggering inflammation within the body.

'What we are learning is that sleep modulates the production of cells that are the protagonists – the main actors – of inflammation.' said Professor Filip Swirski, the study's senior author and director of the Cardiovascular Research Institute at Icahn School of Medicine at Mount Sinai.

Adequate sleep was considered to be between seven and eight hours a night for an adult. The study, published in the Journal of Experimental Medicine, found changes to the methylation of the HSCs' DNA and higher levels of monocytes in the blood of 14 human volunteers when their sleep was shortened to six and a half hours a night for six weeks compared to when they slept for eight hours a night for the same period of time. HSCs and monocytye levels were extracted from blood samples taken during the fifth and sixth weeks of each period and compared.

In addition, blood was sampled from mice, half of whom had their sleep interrupted midway for 16 weeks, and analysed against samples taken ten weeks after the sleep deprived mice were allowed to return to uninterrupted sleep. The genetic changes to HSCs were seen in the mice after sixteen weeks of interrupted sleep and after the mice returned to uninterrupted sleep for ten weeks, although the changes to the epigenome are not considered to be permanent.

'Our findings suggest that sleep recovery is not able to fully reverse the effects of poor-quality sleep. We can detect a molecular imprint of insufficient sleep in immune stem cells, even after weeks of recovery sleep. This molecular imprint can cause the cells to respond in inappropriate ways leading to inflammation and disease.' said Dr Cameron McAlpine, co-lead investigator.

This research may provide a basis to understanding how deprived sleep and thus inflammation can play a role in the development of prevalent diseases.

Previous studies had highlighted how genetic mutations to HSCs can affect the differentiation of HSCs which in some cases can cause clonal haemotopoesis, a condition that can increase the risk of heart disease and some types of blood cancer (see BioNews 1153). This current study has shown sleep restriction affects the differentiation of the HSCs due to changes in the epigenome, and therefore the genetic expression taking place in the cells.

'The mechanistic insight from this study supports findings from larger population studies, which have shown that sleep can have a protective effect against a variety of conditions, including heart disease, cancer, and dementia.' said Dr Marishka Brown, director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute, Bethesda, Maryland, who was not involved in the study.