By Nicole Zhao ’20

Numerous pathological conditions such as obesity, diabetes, cancer, and cardiovascular disease have been connected to insufficient or interrupted sleep. However, little is known about the specific mechanisms by which sleep maintains health. In this study, it was found that sleep regulates hematopoiesis and protects against atherosclerosis in mice. Hematopoiesis is the process of forming blood cellular components from stem cells. Research has confirmed that increased activity of hematopoiesis is an indicator of cardiovascular disease. On the other hand, atherosclerosis is a condition that leads to the hardening and restriction of blood vessels, which contribute to a wide range of cardiovascular diseases.

Using a mouse model, researchers have found that mice subjected to chronic sleep fragmentation had more myeloid white blood cells in their aortas, developed larger atherosclerotic lesions, and produced less hypocretin. Hypocretin is a hypothalamic neuropeptide that has an important role in regulating sleep and arousal (1). It was found that the mechanism by which hypocretin controls myelopoiesis, the formation of myeloid white blood cells, was by restricting the production of CSF1 (colony stimulating factor 1) by premature neutrophils in the bone marrow. CSF1 is a cytokine that plays an essential role in the regulation of survival, proliferation, and differentiation of hematopoietic stem cells (3). However, only premature neutrophils that expressed the hypocretin receptor were responsive to hypocretin regulation of CSF1 (1).

This mechanism was further confirmed in mice with or without hypocretin and its receptor. In hypocretin-null and hypocretin-receptor-null mice, researchers observed an increased number of myeloid white blood cells and accelerated atherosclerosis. Under the same conditions, sleep-fragmented mice with haematopoietic CSF1 deficiency or hypocretin supplementation exhibited reduced numbers of circulating myeloid white blood cells and smaller atherosclerotic lesions. Therefore, there is an inverse relationship between hypocretin levels and myelopoiesis by controlled production of CSF1, with the determining factor being that the premature neutrophils contain hypocretin receptors. This study emphasized the importance of continuous sleep in hematopoiesis and the prevention of atherosclerosis. Moreover, an internal mechanism was identified on how sleep biologically affects one’s health.
References

1. C. McAlpine, et. al., Sleep modulates hematopoiesis and protects against atherosclerosis. Nature 556, 383-387 (2019). doi: 10.1038/s41586-019-0948-2.  
2. J. Groh, et. al., Colony-stimulating factor-1 mediates macrophage-related neural damage in a model for Charcot-Marie-Tooth disease type 1X. Brain 135 (Pt 1), 88-104 (2011). doi: 10.1093/brain/awr283.  
3. Image retrieved from: https://www.flickr.com/photos/pennstatelive/43653755251