Periodic Reporting for period 3 - EMERGE (Epigenetic and metabolic regulation of endothelial heterogeneity)
Okres sprawozdawczy: 2021-03-01 do 2022-04-30
The inner lining of these networks is formed by a single layer of endothelial cells (ECs), which specializes according to the needs of the tissue it supplies (Figure 1). For instance, ECs in the brain are sealed by specialized junctions to form the highly selective blood-brain-barrier, whereas ECs in the liver, kidney, and spleen are discontinuous and have pores to enable the rapid exchange of fluids, particles, and cells. The multitude of phenotypes ECs can adopt suggests substantial plasticity and indicates that heterogeneity is a central endothelial property that allows ECs to execute their multiple tasks. However, the molecular basis of endothelial heterogeneity remains largely unknown.
EMERGE addresses this research problem by studying the relationship between metabolism, epigenetics, and cellular differentiation. EMERGE posits that organ-specific differences in endothelial metabolic state, through altered epigenetics, promote specialization and thereby contribute to heterogeneity within the vascular system. The hypothesis rests on the notion that many of the enzymes that erase epigenetic modifications (from DNA and histones) are exquisitely sensitive to changes in metabolism as they utilize co-substrates that are generated by cellular metabolism.