Spatial, molecular and functional characterization of organ-specific lymphatic endothelial progenitor cells

• Applicant: Dr. Simon Stritt
• Subject Area: Developmental Biology ; Cell Biology
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 377538279

The lymphatic vasculature controls fluid homeostasis, transport of lipids, antigens, and immune cells. Hence it plays central roles in lipid metabolism, tumor metastasis and immunity and consequently the lymphatic system is implicated in the pathogenesis of common diseases such as obesity, autoimmunity, atherosclerosis and cancer. Recently, novel, non-venous-derived lymphatic endothelial progenitor cells (LEPCs) that contribute to the formation of organ-specific lymphatic vasculatures, e.g. in the mesentery, have been identified. I hypothesize that the embryonic origin defines molecularly and functionally distinct LEC populations, and that defects in one of the LEPC populations may account for the organ-specific manifestation of lymphatic dysfunction in primary lymphedema.In the proposed project genetic lineage tracing using novel reporter strains, state of the art imaging, fluorescence-activated cell sorting and single cell sequencing will be applied to decipher the precise spatial origin, function as well as the molecular identity of mesenteric LEPCs. Comparison of the gene expression profiles of non-venous and venous-derived LEPCs and LECs may reveal LEPC-specific genes that potentially determine the distinct functions of the mesenteric lymphatic vasculature. The role of one or two in vitro validated signature genes in the formation and function of the mesenteric lymphatic vasculature will be investigated in vivo using transgenic mouse models. This work will identify the precise origin(s), translocation mechanisms as well as molecular and functional differences between organ-specific LEPCs. Together these results may uncover molecular and cellular mechanisms regulating and determining organ-specific lymphatic vessel development as well as function that could serve as basis for the development of novel therapeutic strategies for the treatment of diseases associated with lymphatic dysfunction.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Professorin Dr. Taija Mäkinen, Ph.D.