The lymphatic vascular system is essential for the maintenance of normal physiology, playing key roles in tissue fluid homeostasis, immune cell clearance and lipid absorption. The innermost layer of this network is comprised of lymphatic endothelial cells, which form a specialised epithelium with important roles in organ development, homeostasis and regeneration. In spite of these critical functions, the cellular mechanisms underpinning the formation of lymphatic endothelial cells have been debated for over a century.
In a recent study published in Nature Cardiovascular Research, the Stone group has shed light on this process, identifying a direct progenitor for lymphatic endothelial cells and providing a cellular blueprint for the formation of lymphatic vessels.
During formation of the vertebrate vasculature, endothelial cells were traditionally thought to emerge from a common pool of progenitor cells that diversify through iterative steps of differentiation to form subtypes of vessels. Lymphatic endothelial cells were thought to represent a striking example of this process, forming via transdifferentiation of venous endothelium. The new research from the Stone Group challenges this view, showing that mammalian lymphatic endothelial cells are derived from a specialised population of lymphatic progenitors. Using single-cell genomics and lineage-tracing, they identified paraxial mesoderm-derived progenitors that directly generate lymphatic endothelial cells. Additional analyses of lymphatic growth, migration, and genetic mutants confirmed these findings, highlighting the role of distinct mesenchymal progenitors in creating specialized endothelial subtypes
Oliver Stone comments, ‘These findings are very exciting for us. In particular, it appears that rather than being an exceptional feature of lymphatic endothelial cells, molecularly distinct progenitors for different vessel types may underpin the establishment of diversity across vascular networks. Our ongoing work aims to understand more about how different types of endothelial cells are formed, with the ultimate goal of engineering subtypes of human endothelial cells for vascularisation of bioengineered tissues.’
The full study, Direct specification of lymphatic endothelium from mesenchymal progenitors, can be read here