It is known that the intestinal lining needs to regenerate daily to be a powerful barrier to counter pathogens while allowing nutrients to be absorbed. The responsibility for this comes from the intestine’s stem cells. They need to meet a level of constant replenishment and repair. But, for this to happen, the stem cell needs to decide if the conditions of the intestine are receptive. If the stem cell makes the wrong decision or coordinates it poorly, intestinal cancer or diseases could occur.
From new research, it has been suggested that intestinal stem cells get cues from the surrounding area to decide what to do. They can then coordinate their activity over tissue through vasculature networks in the same area.
The team discovered that lymphatic capillaries, which are fine vessels responsible for transporting immune cells and draining tissue fluids, are a signaling station that communicate to the stem cell in order to control their action. From lymphatic molecular guidance, the stem cell produces daughter cells that can either self-renew to add to the reserve of stem cells or repopulate the intestinal lining.
The discoveries help understand how primary intestinal components communication disruption may add to intestinal disorders such as inflammation of the bowel. The solution to treating various diseases will be to find out who communicates with whom in this ecosystem and how it is able to reset communication networks.
Stem cells of the intestine live in crypts that reside at the bottom of thickly packed depressions in the lining of the intestine. The stem cells can stay in the crypt through renewal, or form into cells that are differentiated into specialized cells that can migrate out of the crypt replenishing the lining of the gut. In order to discern how a stem cell can balance self renewal with differentiation, there needs to be a complete profile of crypt niches.
In order to analyze the crypt, the researchers utilized various techniques which included single cell and spatial transcriptomics, allowing the team to identify types of cells at certain locations to study their signaling molecules. Results indicated that lymphatic capillaries will assemble a personal connection to the stem cells contained in the crypt and produce a variety of proteins which are crucial for their function.
One earlier protein, REELIN, appeared to be the main candidate for negotiating communication between stem cells and lymphatics. Through manipulation of the amount of REELN in laboratory grown organoid cultures in some of the experiments and genetically suppressing it in mice in other experiments, the team found the REELIN specifically controls the regenerative behavior of the stem cells in the intestine.
The lymphatic system involvement of the stem cells function is a new concept. An earlier study by the team disclosed that lymphatics are also involved closely with skin stem cells and play a crucial role in their regeneration. This leads to the suggestion that the lymphatics could be a core feature of niches of stem cells, however, their relationship to stem cells are probably tailored to the requirements of each tissue.
To view the original scientific study click below:
Lymphatics act as a signaling hub to regulate intestinal stem cell activity