Epigenetic and metabolic regulation of endothelial heterogeneity

Projektinformationen

EMERGE

ID Finanzhilfevereinbarung: 773047

DOI

10.3030/773047

Projekt abgeschlossen

EK-Unterschriftsdatum 6 Februar 2018

Startdatum 1 März 2018

Enddatum 29 Februar 2024

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 998 750,00

EU-Beitrag

€ 1 998 750,00

Koordiniert durch

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Germany

Periodic Reporting for period 4 - EMERGE (Epigenetic and metabolic regulation of endothelial heterogeneity)

Berichtszeitraum: 2022-05-01 bis 2024-02-29

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Scientists have increasingly recognized that the cells lining blood vessels, known as endothelial cells, exhibit considerable diversity in different parts of the body, both in normal and diseased conditions. This diversity influences the architecture, structure, and function of blood vessels. For example, endothelial cells in the brain are sealed by specialized junctions to form the highly selective blood-brain barrier. In contrast, endothelial cells in the liver, kidney, and spleen are discontinuous and have pores to enable the rapid exchange of fluids, particles, and cells. The varied forms that endothelial cells take on suggest they are highly adaptable, indicating that their diversity is a key feature that allows them to perform specific tasks in different tissues. However, the molecular basis for tissue-specific endothelial differentiation and heterogeneity remains largely unknown.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

The EMERGE project investigated the impact of environmental context on endothelial specialization, focusing on the emerging relationship between metabolism, epigenetics, and cellular differentiation. The researchers hypothesized that organ-specific differences in the metabolic state of endothelial cells, through changes in epigenetics, promote specialization and thereby contribute to the diversity seen within the vascular system. This hypothesis is based on the idea that many enzymes that erase epigenetic modifications (from DNA and histones) are extremely sensitive to changes in metabolism, as they utilize co-substrates generated by cellular metabolism.

Using a combination of advanced genetic techniques, high-resolution imaging, metabolomics, and biochemistry, the EMERGE team studied the role of these epigenetic mechanisms in general and organ-specific blood vessel formation and determined how these mechanisms are regulated by environmental signals. Furthermore, they explored whether metabolic changes in disease conditions impact the maintenance of endothelial specialization, potentially causing endothelial dysfunction and tissue degeneration.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

By addressing these objectives, the EMERGE project provided fundamental insights into how nutrients, metabolites, and epigenetic states control vascular growth, differentiation, and function. The collective knowledge gained from these studies helped establish a conceptual framework to explain how tissue-specific environments guide vascular development and how deviations from this process can lead to disease.

Illustration of endothelial heterogeneity