#	Pagina
attuale pagina	/open-h2020/projects/194473/results.html

Report

Teaser, summary, work performed and final results

Periodic Reporting for period 3 - LYMPHORG (Organ-specific mechanisms of lymphatic vascular development and specialisation)

Teaser

Summary

Pathological lymphatic diseases mostly affect vessels in specific tissues, yet organ-specific regulation of lymphatic development and function remain unexplored. This project aims to identify genes and mechanisms regulating organ-specific lymphatic vascular development and explore the therapeutic potential of our newly identified tissue-specific lymphatic endothelial progenitor cell (LEPC). This work is expected to generate novel fundamental understanding of vascular bed-specific mechanisms of lymphatic development and identify a progenitor cell that may be exploited to restore lymphatic function in disorders associated with lymphatic vessel failure. The objectives of this project are to: 1) elucidate molecular mechanisms underlying organ-specific lymphatic vessel formation; 2) determine organ-specific origin(s) of lymphatic vasculature, and 3) determine physiological functions and therapeutic potential of LEPC.

Work performed

We have established methodology and genetic tools for studying (mesenteric) LEPCs and the process of lymphvasculogenesis. The main achievement during the last period is the acquisition of data from single cell RNA sequencing of LECs of mouse embryonic mesenteries, which will be utilized to identify the (mesenteric) LEPC specific transcriptome. In addition, we have developed and characterized novel transgenic models and methodology for the purpose of targeting and studying non-venous derived LEPCs and the lymphvasculogenic process of vessel formation in vivo and ex vivo.

Final results

Single cell transcriptome data generated for LECs of early embryonic mesenteries will now be compared to that obtained for LECs of other tissues of adult mice and embryos in order to identify (mesenteric) LEPC specific signatures. New methodology and genetic tools have been established to allow reconstruction of early mesenteric vascular development and dynamic studies of lymphvasculogenic vessel formation ex vivo. Together these data and tools will allow studying the functional properties of non-venous derived LEC progenitors.