The Rockefeller scientists discovered that lymphatic capillaries — small vessels that transport immune cells and drain fluid from tissues — represent a signaling center that communicates with stem cells to regulate adjust their operations. With molecular guidance from the lymphatic system, stem cells produce daughter cells to regenerate the intestinal lining or renew themselves to replenish their stem cell reserves.
“The key to treating these diseases is figuring out who’s talking to whom in this ecosystem and how we can design it,” said Rachel Niec, a clinical scholar in Elaine Fuchs’ lab. re-establish communication networks”.
Communication in the gut
Intestinal stem cells reside in so-called crypts, which are found at the base of dense depressions in the intestinal lining. Stem cells can renew and stay in the crypt, or differentiate into specialized cells, which then migrate out of the crypt to replenish the intestinal lining. “To understand how stem cells balance self-renewal with differentiation, we need a more complete picture of the crypt niches,” said Marina Schernthanner, a PhD student at the Fuchs lab. .
To zoom in on the catacombs, the team used a suite of techniques, including single-cell and spatial transcription, that allowed them to identify cell types at specific sites and study the molecules. their signal. The results showed that the lymphatic capillaries, which form an intimate connection with stem cells in the crypt, produce several proteins considered important for stem cell functioning.
A previously underappreciated protein, REELIN, emerged as a leading candidate to mediate communication between lymph and stem cells. By manipulating the amount of REELIN in lab-grown intestinal organoid cultures in some experiments and genetically inhibiting it in mice in others, the researchers found that REELIN directly governs regenerative behavior of intestinal stem cells.
Involvement of the lymphatic system in stem cell activity is a relatively new concept. A previous study by the Fuchs group revealed that lymph is also closely related to the skin’s stem cells and plays an important role in hair regeneration. There, however, it is the hair follicle stem cells that signal to the lymphatic capillaries. By controlling their interaction with lymph, stem cells synchronize hair regeneration throughout the tissue. “This suggests that lymph may be a conserved feature of stem cell niches, but their relationship to stem cells may be tailored to the needs of individual tissues,” says Niec.