Work package leader : UPPSALA UNIVERSITET
Architecture of the collecting vessels in the adipose tissue
Lymphedema consist in a lymphatic dysfunction of the superficial capillary network associated with a drainage defect by the deeper collecting plexus. Whereas lymphatic capillaries have been extensively described in the literature, poorly is known about the collectors. It is established that VEGFC controls the lymphatic capillaries, but the factor responsible for collecting vessel function is unclear.
WP2 main objective consists in an extensive description of the poorly investigated lymphatic collecting vessels located in the adipose tissue. We plan to identify a specific signature of the lymphatic in the adipose tissue: molecular and cellular.
Partner 4 (UU) is an expert in the identification of the lymphatic network during embryonic development. In this part of the proposal, they will investigate the lymphatic network in the adult in mouse models from Partner 1 (Inserm) and Partner 2 (UnivHel). Dr Tatin (partner 1 lab) was a postdoctoral fellow of partner 4 and developed a scientific bridge between these two laboratories by developing collaborations aiming to study the role of cell planar polarity in the collecting vessels valve formation. Here, they plan to go further in the study of these collecting vessels by developing original mice models and transparisation technics to better study the vessel formation and stability by confocal microscopy.
Partner 1 will have access to liposuctions from women who developed lymphedema to pursue this study on human tissues. The first challenge will be to establish a valid protocole to isolate/purify adipose tissue lymphatic endothelial cells based on the markers obtained in this WP. This WP will determine gene regulation modifications in the lymphedematous arm compared to the opposite control arm on the same patient.
In parallel, data obtained will be compared to those previously obtained by partner 5 (DDUV). Partner 5 laboratory possesses extensive clinical data on patients with primary lymphedema, with large-scale genotyping data generated using cutting-edge Next Generation Sequencing techniques and a state-of-the-art data analysis pipeline developed in-house. The secondary objective of WP2 will be to determine whether primary and secondary lymphedema could involve similar gene expression modulations.
We are determined to find a treatment.